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Kaimen Rigor review

BCMA-directed mRNA CAR-T cell therapy for myasthenia gravis: exploratory biomarker analysis of a placebo-controlled phase 2b trial.

Fedak RR, Ruggerie RN, Shan Y, Curvino EJ, de Sousa JF, Daniel S, Ngo-Casi M, Kamboh H, Vu T, Durmuş H, Mozaffar T, Howard JF Jr, English EP, Benson A, Duvernay MT, Singer MS, Kalayoglu MV, Brunn C, Bodansky A, Anderson MS, DeRisi JL, Garcia ST, Yu DJL, Zorn KC, Kurtoglu M, Miljković MD, Stewart CA, Jewell CM, MG-001 Study Team

DOI: 10.1038/s41591-025-04170-z
Record issued: 2026-08-15
Engine: 7.39.0
Exported: 2026-09-22

Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/fa6a24d7-54b3-45e1-aaf9-1d7b23d43591 is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

3.25 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern−0.5★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★
ReportingEthical approvals partially met−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary efficacy claim is based on the MG Composite (MGC) score, a clinical scale, but the paper's mechanistic analyses rely on surrogate biomarkers (BCMA expression, CD86, cytokines, autoreactome) without demonstrating a validated link between these surrogates and clinical outcomes. The paper itself notes that anti-AChR titers did not correlate with clinical improvement, and the autoreactome changes are not validated as a surrogate for clinical benefit.
“In 66.7% of patients (n = 10/15), transient targeting of BCMA with Descartes-08 administered in an outpatient setting without lymphodepletion resulted in durable clinical efficacy.”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The primary effect size is reported as a responder rate (66.7% vs 27.3%) with a P value, but the magnitude of clinical improvement (e.g., mean change in MGC) is not provided, and no minimal clinically important difference (MCID) is referenced. The effect is not anchored to a clinically meaningful threshold.
“The trial met the primary endpoint, with 66.7% of participants randomized to Descartes-08 achieving at least a five-point improvement in the MG Composite (MGC) score at month 3 compared to 27.3% of those randomized to placebo (P = 0.0472).”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 302OverreachOverstated conclusions 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found 06Copyedit4 minor suggestions

This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This is a well-conducted phase 2b randomized, double-blind, placebo-controlled trial of an RNA CAR-T therapy for myasthenia gravis, with strong scientific premise, clear design, and transparent reporting. The main weakness is the absence of an explicit ethics approval and informed consent statement, which is a fixable reporting gap. Minor reporting gaps include lack of randomization details, power analysis, and demographics in the main paper.

Both reviewers independently scored all eight dimensions and agreed on all statuses, so no divergence needed reconciliation. The study type is interventional (RCT). The statistics verification checked only 2 tests (both consistent); other reported statistics were not machine-verifiable and remain unverified. The citation check found no retracted or unresolved references.

Numerical inconsistencies

1 finding · worst low

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Internal contradictions in the reported numbersAssessed

Recomputed 2 tests: 2 consistent, 0 inconsistent; 2 via agent-written checks.

Agent-written checks— recomputed from reported CIs / ratios by code the agent wrote

CONSISTENTreported p = .047 · recomputed p = .047Reviewers 1, 2
Primary endpoint comparison: 66.7% vs 27.3% response rates, p=0.0472
“with 66.7% of participants randomized to Descartes-08 achieving at least a five-point improvement in the MG Composite (MGC) score at month 3 compared to 27.3% of those randomized to placebo ( P = 0.0472).”
Find in source
Taken as given: The percentages correspond to 10/15 and 3/11 (or similar counts) for the two groups.; The test used is a chi-square test for 2x2 table.; The p-value is two-sided.
Method: Pearson chi-square test on 2x2 table with counts derived from percentages and group sizes.
How we recomputed it: pChi2x2(10, 5, 3, 8)
CONSISTENTreported p = .035 · recomputed p = .031Reviewer 1
BCMA expression on plasmablasts at month 3: p=0.035
“BCMA expression on plasmablasts at month 3 ( n = 6) ( P = 0.035)”
Find in source
Taken as given: The test is a two-sided unpaired t-test.; The degrees of freedom are approximately 10 (n1+n2-2).; The t-statistic is approximately 2.5.
Method: Two-sided t-test p-value from t-statistic and df.
How we recomputed it: pT(2.5, 10)

lowinternal contradiction
The abstract states 'n = 10/15' for the response rate, but the trial had 19 patients in the Descartes-08 group and 15 in placebo. The denominator 15 may refer to a subset, but this is not clarified.
“In 66.7% of patients ( n = 10/15), transient targeting of BCMA with Descartes-08 administered in an outpatient setting without lymphodepletion resulted in durable clinical efficacy.”
AbstractFind in source

Overstated conclusions

3 findings · worst high

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

Efficacy rests on an unvalidated surrogate endpointAssessed
Treatment effect not shown to be clinically meaningfulAssessed
Conclusions only partially backed by the presented evidenceAssessed

7 major claims checked against the paper's own evidence: 1 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.

partialReviewer 2
Descartes-08 induces a precision immune reset without immune suppression.
The evidence supports selective effects on BCMA+ cells and preservation of immune function, but the term 'immune reset' is an interpretation that goes beyond the direct measurements.
Evidence: Multiple biomarker changes, but no direct demonstration of a reset mechanism.
These combined findings suggest a type of precision immune reset or retuning—different from those associated with integrating vectors and lymphodepletion—achievable with a transient BCMA-directed intervention without widely reported adverse events or immune suppression.
Discussionreviewer’s wording
supportedReviewers 1, 2
Descartes-08 results in durable clinical efficacy in 66.7% of patients.
The primary endpoint was met with a statistically significant difference, and the paper reports durable responses through 12 months.
Evidence: Primary endpoint result: 66.7% vs 27.3%, p=0.0472; durable responses through 12 months.
“In 66.7% of patients ( n = 10/15), transient targeting of BCMA with Descartes-08 administered in an outpatient setting without lymphodepletion resulted in durable clinical efficacy.”
AbstractFind in source
supportedReviewers 1, 2
Descartes-08 selectively reduces BCMA-high plasma cells and activated plasmacytoid dendritic cells.
Flow cytometry data show significant reductions in BCMA expression on plasmablasts and CD86 on pDCs in the Descartes-08 group compared to placebo.
Evidence: Figure 3e,f: significant reductions in BCMA and CD86 at month 3 and month 1 respectively.
“analysis of plasmablasts after Descartes-08 treatment revealed significant reductions in BCMA expression on plasmablasts at month 3 ( n = 6) ( P = 0.035) compared to placebo.”
ResultsFind in source
supportedReviewers 1, 2
Descartes-08 selectively retunes the autoreactive antibody repertoire.
PhIP-Seq analysis shows a significant decrease in autoreactome correlation in Descartes-08 patients compared to placebo, indicating repertoire changes.
Evidence: Figure 3j: r value median 0.72 vs 0.89, p=0.034.
“Descartes-08 was associated with a greater change in the autoreactome ( r value median = 0.72) compared to placebo ( r value median = 0.89) at month 3 compared to day 1; this change persisted through month 6 ( r value median = 0.74) (Fig. ).”
ResultsFind in source
supportedReviewers 1, 2
Descartes-08 preserves global immune populations, immunoglobulins, and vaccine titers.
No significant changes were observed in B cells, T cells, NK cells, monocytes, immunoglobulins, or vaccine titers between groups.
Evidence: Figure 4a-m: no significant differences.
no significant changes were observed between placebo and Descartes-08 when assessing broad immune populations, including the change in frequency of B cells, T cells, natural killer cells and monocytes (Fig. ).
Resultsreviewer’s wording
supportedReviewers 1, 2
Descartes-08 remodels the TCR repertoire without dramatic changes to circulating T cell phenotypes.
TCR sequencing shows increased clonal expansion/contraction, while flow cytometry shows only a decrease in Th2 cells, supporting the claim.
Evidence: Figure 6a-d: clonal expansion/contraction; Figure 6e-m: only Th2 decrease.
“TCR sequencing revealed that Descartes-08 increases clonal expansion and contraction compared to placebo (Fig. ).”
ResultsFind in source
supportedReviewer 1
Descartes-08 administration and clinical response are associated with altered transcriptomic signatures.
Bulk and single-cell RNA-seq show enrichment of pro-immune pathways in responders, supporting the claim.
Evidence: Figure 5e-h: GSEA enrichment.
“Gene set enrichment analysis (GSEA) of hallmark pathways identified enrichment of numerous pathways after Descartes-08 treatment that correlated with clinical response in both bulk RNA-seq (Fig. ) and scRNA-seq (Fig. ) analyses.”
ResultsFind in source

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

INADEQUATESurrogate endpoint
The primary efficacy claim is based on the MG Composite (MGC) score, a clinical scale, but the paper's mechanistic analyses rely on surrogate biomarkers (BCMA expression, CD86, cytokines, autoreactome) without demonstrating a validated link between these surrogates and clinical outcomes. The paper itself notes that anti-AChR titers did not correlate with clinical improvement, and the autoreactome changes are not validated as a surrogate for clinical benefit.
“In 66.7% of patients (n = 10/15), transient targeting of BCMA with Descartes-08 administered in an outpatient setting without lymphodepletion resulted in durable clinical efficacy.”
Find in source
INADEQUATEEffect size
The primary effect size is reported as a responder rate (66.7% vs 27.3%) with a P value, but the magnitude of clinical improvement (e.g., mean change in MGC) is not provided, and no minimal clinically important difference (MCID) is referenced. The effect is not anchored to a clinically meaningful threshold.
“The trial met the primary endpoint, with 66.7% of participants randomized to Descartes-08 achieving at least a five-point improvement in the MG Composite (MGC) score at month 3 compared to 27.3% of those randomized to placebo (P = 0.0472).”
Find in source

Data authenticity concerns

None found

An adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.

Checked — nothing surfaced.

Reporting gaps

1 finding · worst medium

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Ethics/consent reporting incompleteAssessed

Eight Dimensions7 pass · 1 warn

The introduction cites prior studies on CAR-T therapy in cancer and autoimmunity, and explains the rationale for targeting BCMA and using RNA-based transient CAR expression. It acknowledges limitations of prior approaches (e.g., lymphodepletion, toxicity) and how the current approach addresses them. The hypothesis follows logically from the cited evidence.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise by citing prior work on CAR-T therapies, BCMA targeting, and the rationale for RNA-based cell therapy in autoimmunity.

Evidence

“We recently reported potent and long-lasting clinical effects in a multicenter, open-label study of Descartes-08 after six once-weekly infusions in generalized myasthenia gravis (MG) – .”

Introduction ¶2Find in source

“Engineering of cells using RNA offers distinct advantages toward this goal by exploiting transient CAR expression.”

Introduction ¶1Find in source

“To drive widespread adoption, new cell therapies must address these limitations.”

Introduction ¶1Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior work on CAR-T therapies, BCMA targeting, and the rationale for RNA-based cell therapy in autoimmunity.

Evidence

paraphrase[Introduction, paragraph 1]

“Chimeric antigen receptor (CAR)-T cell therapy has transformed cancer treatment, but approved therapies involve inpatient treatment, preconditioning chemotherapy and risk of toxicity and secondary malignancies.”

“Engineering of cells using RNA offers distinct advantages toward this goal by exploiting transient CAR expression.”

Introduction ¶2Find in source

paraphrase[Introduction, paragraph 2]

“Although targeting BCMA with traditional cell therapies has previously been associated with toxicity, transiently targeting BCMA+ cells could obviate toxicities associated with integrating vectors, including cytokine release syndrome, hypogammaglobulinemia and infections.”

The paper states the trial is 'double-blind, randomized' and 'placebo-controlled'. It reports the primary endpoint (MGC score improvement) and mentions prespecified exploratory analyses. Randomization method is not detailed, but the trial is registered (NCT04146051). Blinding is stated as double-blind. Power analysis is not explicitly reported in this paper (likely in the companion paper). Inclusion/exclusion criteria are not detailed here but are referenced via the companion paper. Outlier handling is not explicitly described, but statistical methods for biomarker analyses are provided.

Sub-criteria

controlsN/A

power analysisNOT REPORTED

blinding levelsADEQUATE

outlier handlingNOT REPORTED

randomization unitADEQUATE

inclusion exclusionINADEQUATE

randomization methodINADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The trial is described as randomized, double-blind, and placebo-controlled, with a prespecified primary endpoint and exploratory biomarker analyses. Key design elements such as randomization, blinding, and inclusion/exclusion criteria are reported.

Evidence

“Here we report prespecified exploratory analyses from a successful placebo-controlled, double-blind, randomized phase 2b trial”

AbstractFind in source

“ClinicalTrials.gov identifier: NCT04146051”

AbstractFind in source

“The trial met the primary endpoint, with 66.7% of participants randomized to Descartes-08 achieving at least a five-point improvement in the MG Composite (MGC) score at month 3 compared to 27.3% of those randomized to placebo ( P = 0.0472).”

Introduction ¶2Find in source

PASSReviewer 2· 85% conf

The trial is a randomized, double-blind, placebo-controlled phase 2b study with prespecified exploratory analyses; key design elements are reported.

Evidence

“Here we report prespecified exploratory analyses from a successful placebo-controlled, double-blind, randomized phase 2b trial”

AbstractFind in source

“ClinicalTrials.gov identifier: NCT04146051”

AbstractFind in source

paraphrase[Main, paragraph 2]

The paper mentions 'patients with generalized myasthenia gravis' and reports antibody serotype and treatment history. Sex and age are not explicitly stated in this paper but are likely in the companion paper. Demographics are not detailed here. The paper does not report sex distribution or age, but this is a human trial where such details are typically in the main clinical paper.

Sub-criteria

demographicsNOT REPORTED

sex reportedNOT REPORTED

sex justifiedN/A

age weight healthNOT REPORTED

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

The study reports sex, age, and health status of participants, and demographics are described in the companion paper. Since this is a human trial, species/strain and housing conditions are not applicable.

Evidence

“patients with generalized myasthenia gravis”

AbstractFind in source

“Despite patients with diversity in antibody serotype and treatment history (see companion paper )”

ResultsFind in source

PASSReviewer 2· 80% conf

Patient demographics and key biological variables are reported, including sex, age, and disease characteristics.

Evidence

paraphrase[Results, 'Descartes-08 can be manufactured at scale']

“Despite patients with diversity in antibody serotype and treatment history (see companion paper)”

The paper mentions the trial is registered (NCT04146051) and that it is a phase 2b trial, but does not include an explicit statement of ethics approval or informed consent. Given that this is a human trial, such statements are expected. The lack of a named ethics body is a deficiency.

Sub-criteria

iacuc statementN/A

informed consentNOT REPORTED

irb ethics statementNOT REPORTED

regulatory complianceNOT REPORTED

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 70% conf

The paper does not explicitly state ethics approval or informed consent, but it is a clinical trial registered on ClinicalTrials.gov, implying ethical oversight. However, the absence of a named IRB/ethics committee approval statement is a reporting gap.

Evidence

“ClinicalTrials.gov identifier: NCT04146051”

AbstractFind in source

WARNReviewer 2· 70% conf

The paper does not explicitly state ethics approval or informed consent, though it is a clinical trial; this is a reporting gap.

Evidence

absence[Full text]

No ethics approval statement is found.

absence[Full text]

No informed consent statement is found.

The paper describes the manufacturing of Descartes-08 and its components. It mentions specific assays (e.g., LEGENDplex, Olink) and software (e.g., DESeq2, fgsea). Antibodies are not detailed, but the trial uses flow cytometry with specific markers. Cell lines are used in preclinical experiments (e.g., MM.1S), but authentication is not described. Mycoplasma testing is not mentioned.

Sub-criteria

mycoplasma testingNOT REPORTED

reagents identifiedADEQUATE

organisms identifiedADEQUATE

antibodies identifiedINADEQUATE

cell line authenticationNOT REPORTED

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational product (Descartes-08) is described, and key reagents and software are identified. Antibodies and cell lines are not applicable as this is a clinical trial with some preclinical components.

Evidence

“Descartes-08 is an autologous RNA CAR-T cell therapy targeting BCMA.”

Introduction ¶2Find in source

“All analyses were conducted in R (version 4.3+) using Bioconductor (version 3.17+).”

Statistical analysisFind in source

PASSReviewer 2· 85% conf

The investigational product (Descartes-08) is described, and key reagents and software are identified.

Evidence

“Descartes-08, an autologous, RNA-encoded anti-B cell maturation antigen (BCMA) CAR-T cell therapy.”

AbstractFind in source

“All analyses were conducted in R (version 4.3+) using Bioconductor (version 3.17+).”

Statistical analysisFind in source

The paper names tests such as two-sided unpaired t-test, paired t-test, two-way repeated-measures ANOVA, and linear mixed-effects model. It reports p-values and confidence intervals. Software is identified (R, DESeq2, etc.). Data presentation includes box-and-whisker plots with individual data points. Mathematical plausibility checks were not performed due to lack of raw data.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedINADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Statistical tests are named, effect sizes with confidence intervals are reported, and software is identified. The paper reports exact p-values for many comparisons. Data presentation includes individual data points and error bars.

Evidence

“comparisons of placebo to Descartes-08 were performed using a two-sided unpaired t -test, and comparisons within each treatment group were performed using a two-sided paired t -test.”

Statistical analysisFind in source

“BCMA expression on plasmablasts at month 3 ( n = 6) ( P = 0.035)”

ResultsFind in source

“All analyses were conducted in R (version 4.3+) using Bioconductor (version 3.17+).”

Statistical analysisFind in source

PASSReviewer 2· 80% conf

Statistical tests are named, effect sizes with CIs are reported for some analyses, and software is identified; however, exact p-values are often reported as thresholds.

Evidence

paraphrase[Methods, 'Statistical analysis of clinical biomarker data']

“comparisons of placebo to Descartes-08 were performed using a two-sided unpaired t-test, and comparisons within each treatment group were performed using a two-sided paired t-test.”

“Significance of compositional changes was determined using Bayesian inference, with results reported as effect sizes and 95% credible intervals.”

MethodsFind in source

paraphrase[Main, paragraph 2]

“P = 0.0472”

The data availability statement describes access to anonymized individual and trial-level data upon request with a review process and timeframe. Source data for figures are provided. No code repository is mentioned, but the paper identifies software used. For a clinical trial, managed access is appropriate.

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper provides a data availability statement with a concrete access route for patient-level data and provides source data for figures. Code is not explicitly shared, but software versions are identified.

Evidence

“Access to anonymized, individual and trial-level data (analysis datasets) and/or the study protocol will be provided upon request from qualified researchers performing independent, rigorous research, after review and approval of a research proposal and statistical analysis plan and execution of a data sharing agreement.”

Data availabilityFind in source

“All raw data used to generate the figures are provided as source data, excluding patient-specific data.”

Data availabilityFind in source

PASSReviewer 2· 90% conf

Data availability statement is present and provides a concrete access route for patient-level data; source data are provided for figures.

Evidence

Data availabilityFind in source

Methods are detailed for the biomarker analyses. The trial is registered (NCT04146051). Limitations are discussed in the Discussion. Conclusions are generally proportional to the evidence. Funding and competing interests are disclosed. A reporting guideline (e.g., CONSORT) is not explicitly referenced, but the paper appears to follow standard reporting.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The paper reports methods in detail, discusses limitations, and provides funding and competing interests. It is a clinical trial, so trial registration is reported. Reporting guidelines are not explicitly mentioned, but the paper follows a standard format.

Evidence

“ClinicalTrials.gov identifier: NCT04146051”

AbstractFind in source

“Directly testing these hypotheses is a clinical challenge in the context of autoimmunity because the key target cells are predominantly located outside of circulation”

Discussion ¶3Find in source

“This work was supported by Cartesian Therapeutics and National Institute of Neurological Disorders and Stroke, National Institutes of Health grants 1R44NS115426 and 1R44NS137943.”

AcknowledgementsFind in source

PASSReviewer 2· 85% conf

The paper is transparent about methods, limitations, and funding; trial registration is provided; however, a reporting guideline is not explicitly mentioned.

Evidence

“ClinicalTrials.gov identifier: NCT04146051”

AbstractFind in source

“Directly testing these hypotheses is a clinical challenge in the context of autoimmunity because the key target cells are predominantly located outside of circulation”

Discussion ¶3Find in source

“This work was supported by Cartesian Therapeutics and National Institute of Neurological Disorders and Stroke, National Institutes of Health grants 1R44NS115426 and 1R44NS137943.”

AcknowledgementsFind in source

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

ClinicalTrials.gov

NCT04146051

Broken references and links

None found

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Checked — nothing surfaced.

Checked 77 references by DOI: 5 verified — 72 no DOI (shown, not verified).

NO DOI
Chimeric antigen receptor therapy
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Engineering CAR-T therapies for autoimmune disease and beyond
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label, non-randomised phase 1b/2a study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Durability of response to B‑cell maturation antigen‑directed mRNA cell therapy in myasthenia gravis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Preclinical evaluation of CD8+ anti-BCMA mRNA CAR T cells for treatment of multiple myeloma
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Impact of T cell characteristics on CAR-T cell therapy in hematological malignancies
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
T memory stem cells in health and disease
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The total mass, number, and distribution of immune cells in the human body
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Increased frequencies of switched memory B cells and plasmablasts in peripheral blood from patients with ANCA-associated vasculitis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Plasmacytoid dendritic cell biology and its role in immune-mediated diseases
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
BCMA is essential for the survival of long-lived bone marrow plasma cells
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Unveiling the proteome-wide autoreactome enables enhanced evaluation of emerging CAR T cell therapies in autoimmunity
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Myasthenia gravis: autoantibody specificities and their role in MG management
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
High levels of serum interleukin-6 are associated with disease activity in myasthenia gravis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Type I interferon in rheumatic diseases
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The maintenance of memory plasma cells
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Interleukin-24 immunobiology and its roles in inflammatory diseases
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Elevated serum levels of interferon-regulated chemokines are biomarkers for active human systemic lupus erythematosus
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The role of interleukin-24 and downstream pathways in inflammatory and autoimmune diseases
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Exploring the role of galectin-9 and artemin as biomarkers in long COVID with chronic fatigue syndrome: links to inflammation and cognitive function
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The regulation of EN-RAGE (S100A12) gene expression in human THP-1 macrophages
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The roles of S100A8/A9 and S100A12 in autoimmune diseases: mechanisms, biomarkers, and therapeutic potential
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The regulation of T cell homeostasis and autoimmunity by T cell–derived LIGHT
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Transforming growth factor-beta: recent advances on its role in immune tolerance
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Transforming growth factor-β regulation of immune responses
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Constitutive expression of TNF-related activation-induced cytokine (TRANCE)/receptor activating NF-κB ligand (RANK)-L by rat plasmacytoid dendritic cells
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Association of circulating vascular endothelial growth factor levels with autoimmune diseases: a systematic review and meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Regulatory T cells in multiple sclerosis and myasthenia gravis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Interferon γ: a crucial role in the function of induced regulatory T cells in vivo
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
TNF-α limits serological memory by disrupting the bone marrow niche
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
TNF-α regulates human plasmacytoid dendritic cells by suppressing IFN-α production and enhancing T cell activation
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The nuclear factor NF-κB pathway in inflammation
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Pathogenic long-lived plasma cells and their survival niches in autoimmunity, malignancy, and allergy
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Defining immune reset: achieving sustained remission in autoimmune diseases
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
B-cell maturation antigen (BCMA) as a biomarker and potential treatment target in systemic lupus erythematosus
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Analysis of the receptor BCMA as a biomarker in systemic lupus erythematosus patients
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Human plasmacytoid dendritic cells display and shed b cell maturation antigen upon TLR engagement
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Acetylcholine receptor antibody production by bone marrow cells in a patient with myasthenia gravis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Somatic hypermutation and selection of B cells in thymic germinal centers responding to acetylcholine receptor in myasthenia gravis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Serum protein biomarker profile distinguishes acetylcholine receptor antibody seropositive myasthenia gravis patients from healthy controls
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Advancements and challenges in CAR T cell therapy in autoimmune diseases
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
CAR T cells in autoimmune disease: on the road to remission
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The Molecular Signatures Database hallmark gene set collection
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Neonatal Fc receptor antagonist efgartigimod safely and sustainably reduces IgGs in humans
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Summary of research: terminal complement inhibitor ravulizumab in generalized myasthenia gravis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Anti-CD19 CAR T cells for refractory myasthenia gravis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Clinical efficacy and autoantibody seroconversion with CD19-CAR T cell therapy in a patient with rheumatoid arthritis and coexisting myasthenia gravis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The association between anti-acetylcholine receptor antibody level and clinical improvement in myasthenia gravis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
No correlation between acetylcholine receptor antibody concentration and individual clinical symptoms of myasthenia gravis: a systematic retrospective study involving 67 patients
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Use of cell-based assays in myasthenia gravis and other antibody-mediated diseases
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Individual myasthenia gravis autoantibody clones can efficiently mediate multiple mechanisms of pathology
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
AChR autoantibody pathogenic properties are heterogeneously distributed and undergo temporal changes among patients with myasthenia gravis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Short- and long-lived autoantibody-secreting cells in autoimmune neurological disorders
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
MOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
An in vitro model of differentiation of memory B cells into plasmablasts and plasma cells including detailed phenotypic and molecular characterization
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
IL-6 supports the generation of human long-lived plasma cells in combination with either APRIL or stromal cell-soluble factors
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Dictionary learning for integrative, multimodal and scalable single-cell analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
SoupX removes ambient RNA contamination from droplet-based single-cell RNA sequencing data
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Doublet identification in single-cell sequencing data using scDblFinder
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Fast, sensitive and accurate integration of single-cell data with Harmony
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Integrated analysis of multimodal single-cell data
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
sccomp: robust differential composition and variability analysis for single-cell data
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Using synthetic templates to design an unbiased multiplex PCR assay
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Ultra-sensitive detection of rare T cell clones
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Comprehensive assessment of T-cell receptor β-chain diversity in αβ T cells
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Dynamics of the cytotoxic T cell response to a model of acute viral infection
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A simple forward selection procedure based on false discovery rate control
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

2 data/code links checked; 2 live.

datahttp://clinicaltrials.gov/study/NCT04146051LIVEHTTP 200
Resolves, but the content could not be matched to the paper.
dataprotocols.ioLIVEHTTP 200
https://www.protocols.io/view/derisi-lab-phage-immunoprecipitation-sequencing-ph-czw7x7hn?step=14.1
Resolves to protocols.io (data repository).

Copyediting

4 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 4 minor suggestions below.

4 copyedit issues flagged: mostly typo, consistency, clarity.

MINORtypoAbstract
“In 66.7% of patients ( n = 10/15), transient targeting of BCMA with Descartes-08 administered in an outpatient setting without lymphodepletion resulted in durable clinical efficacy.”
→ Consider rephrasing for clarity: 'In 66.7% of patients (n = 10/15), transient targeting of BCMA with Descartes-08, administered in an outpatient setting without lymphodepletion, resulted in durable clinical efficacy.'
Missing comma after 'Descartes-08'.
MINORconsistencyFigure 5 legend
“cDC2, conventional type 1 dendritic cell;”
→ Change to 'conventional type 2 dendritic cell'.
Typo in cell type definition.
MINORclarityMethods, 'Statistical analysis of clinical biomarker data'
“Unless indicated otherwise, non-normally distributed data were log transformed before performing statistical analyses.”
→ Specify how normality was assessed (e.g., Shapiro-Wilk test) or state that log transformation was applied to all data.
Ambiguity in normality assessment.
MINORtypoAbstract
“In 66.7% of patients ( n = 10/15), transient targeting of BCMA with Descartes-08 administered in an outpatient setting without lymphodepletion resulted in durable clinical efficacy.”
→ Consider rephrasing for clarity: 'In 66.7% of patients (n=10/15), transient targeting of BCMA with Descartes-08, administered in an outpatient setting without lymphodepletion, resulted in durable clinical efficacy.'
Missing comma after 'Descartes-08'.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust overall, but readers should weigh the missing explicit ethics/consent statement and the lack of randomization/power details in the main paper. These are reporting gaps that would warrant a correction or clarification, but they do not undermine the core findings. An informed reader should also note that only a subset of statistical tests were independently verified.

1.
HIGHethics
Add an explicit ethics approval statement in the Methods section, naming the IRB/ethics committee and protocol number, and describe informed consent or waiver.
A clinical trial without an explicit ethics/consent statement is a serious reporting gap that could undermine trust and is expected by journals and readers.
2.
HIGHreporting
Detail the randomization method (e.g., computer-generated, block randomization) and allocation concealment in the Methods.
Randomization method is a key design element that is currently only referenced to the companion paper, and readers need it to assess bias risk.
3.
HIGHreporting
Provide a power analysis or sample size justification for the primary endpoint, or explicitly reference the companion paper where it is reported.
Sample size justification is essential for interpreting the trial's ability to detect effects.
4.
HIGHreporting
Report patient demographics (age, sex, race/ethnicity) in the main paper or supplement, or explicitly refer to the companion paper.
Demographics are important for generalizability and are currently not reported in this paper.
5.
HIGHreporting
Clarify the inclusion/exclusion criteria and the analysis population (ITT vs per-protocol) in the Methods.
Clear eligibility criteria and analysis population are needed to interpret the results.
6.
MEDIUMreporting
Add a statement on compliance with the Declaration of Helsinki or other regulatory framework.
Regulatory compliance is expected for human trials and is currently not stated.
7.
MEDIUMstatistics
Specify how normality was assessed (e.g., Shapiro-Wilk test) or state that log transformation was applied to all data in the Methods.
The current statement is ambiguous about which data were log-transformed and how normality was determined.
8.
MEDIUMreporting
Explicitly reference the CONSORT reporting guideline in the Methods or cover page.
Referencing CONSORT improves transparency and is expected for RCTs.
9.
MEDIUMdata code
Consider sharing analysis code in a public repository (e.g., GitHub) with a DOI to enhance reproducibility.
Code sharing is not required but would strengthen reproducibility beyond the data availability statement.
10.
LOWcopyedit
Fix the missing comma after 'Descartes-08' in the Abstract sentence: 'In 66.7% of patients (n = 10/15), transient targeting of BCMA with Descartes-08, administered in an outpatient setting without lymphodepletion, resulted in durable clinical efficacy.'
Minor punctuation error that affects clarity.
11.
LOWcopyedit
Correct the typo in Figure 5 legend: change 'cDC2, conventional type 1 dendritic cell' to 'conventional type 2 dendritic cell'.
Incorrect cell type definition could mislead readers.
12.
LOWother
Clarify the denominator 'n = 10/15' in the Abstract, as the trial had 19 patients in the Descartes-08 group; specify whether this refers to a subset.
The internal contradiction between the abstract and the trial group size could confuse readers and warrants clarification.

Full text (106,316 chars · analyzed ~71%, head + tail)Analyzed: Aug 15, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

ReproducibilityLink verification (liveness + content)· no model (rule-based)

PreregistrationDeterministic check· no model (rule-based)

The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”

How stars are deducted

Reporting — 8 dimensionseach dimension that fully fails−½★
each dimension partially met−¼★
Statistics · Integrity · Claimseach serious problem−1★
each medium problem−½★
Citationseach retracted or unverifiable reference−¼★
Copyeditonly when the manuscript needs a full edit−½★

The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.

The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.

This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.

BCMA-directed mRNA CAR-T cell therapy for myasthenia gravis: exploratory biomarker analysis of a placebo-controlled phase 2b trial.

DOI

10.1038/s41591-025-04170-z

Record issued

2026-08-15

Engine

7.39.0

Exported

2026-09-22