Science brief: a reading aid, unvalidated by any person. Not a prediction and not advice. Public data only.
Science brief: in vivo CAR-T
As of 2025-12-31. Topic mode. Literature: in vivo CAR-T. 50 abstracts read, 24 claims checked, 0 papers had no abstract and were not read.
Read this first.
- Each claim was extracted by a model from one abstract. A second, separate reader then checked it against the abstracts in this pack, and a third checked that reader. Every line below carries two exact quotes that code found in the sources.
- The corpus is each lab's three most recent last-author papers at four year-ends, abstracts only. "No independent support found" means none in this corpus. It never means not replicated.
- The order is a published sort rule (
scirank-v1): highest evidence tier among verified claims, then independent supports, then fewer contradictions. It is not a score and it predicts nothing. - Evidence tier comes from the extraction's model-system field. "Randomized" is a word rule on the abstract.
Measured, once, on planted errors (an upper bound on real ones):
- One pass over the retrieved abstracts found 110 of 121 hard planted misstatements and named the paper that shows each (91%, 95% interval 85 to 96). It flagged 2 of 423 unaltered claims (false alarms).
- By type: a flipped direction 58 of 66 (88%, 81 to 94); a number swapped for another in the same abstract 35 of 37 (95%, 83 to 100); animal and human swapped 17 of 18 (too few for a rate).
- Baselines on the same claims: a read with no literature flagged 52% and could name no paper; the Lens with a string rule found 2%; fan-out over chunks found 89%, not better than one pass.
- Planted errors are an upper bound on real ones: one word or number was changed and the true paper was in the pack. No person has checked a real case. Reader and extractor are both Claude models; scoring was by code against a key.
- Supported records, the framed read and the ranking are not measured by this test.
Supported records, graded in session by two blind agents (20 drawn from real briefs, both graders must agree): 20 of 20 held (83% to 100%). The same graders rejected 20 of 20 controls that code built to disagree with their own paper. Model-graded, not human-verified: docs/methodology/scibrief-grading.md.
Extraction: Measured accuracy on a fresh sample (agent readers, both must agree): output_type right 97% (92%–99%); model_system right 95% (90%–98%); scale right 97% (93%–99%); claim supported 98% (94%–99%); effect numbers supported 99% (92%–100%); limitations supported 93% (85%–97%).
Where a paper disagrees with a claim
None found in this pack.
Labs by strength of evidence
| # | Lab | Top tier among verified claims | Verified claims | Independent supports | Contradictions | Lens order | Company, PI named on the filing |
|---|---|---|---|---|---|---|---|
| 1 | Donald M. O’Rourke, University of Pennsylvania | human | 2 of 2 | 0 | 0 | 3 | none found |
| 2 | Terry J. Fry, University of Colorado Anschutz | animal | 3 of 3 | 0 | 0 | 1 | none found |
| 3 | Wayne Anthony Marasco, Harvard University | animal | 2 of 2 | 0 | 0 | 4 | none found |
| 4 | Xianxin Hua, University of Pennsylvania | animal | 2 of 2 | 0 | 0 | 5 | none found |
| 5 | Nicola J. Mason, University of Pennsylvania | animal | 2 of 2 | 0 | 0 | 6 | none found |
| 6 | Hideho Okada, University of California, San Francisco | animal | 2 of 2 | 0 | 0 | 8 | none found |
| 7 | Stanley R. Riddell, University of Washington | animal | 2 of 2 | 0 | 0 | 9 | none found |
| 8 | Anjie Zhen, University of California, Los Angeles | animal | 1 of 2 | 0 | 0 | 2 | none found |
| 9 | Soheil Meshinchi, University of Washington | animal | 1 of 2 | 0 | 0 | 7 | none found |
| 10 | Samuel K. Lai, University of North Carolina at Chapel Hill | animal | 1 of 1 | 0 | 0 | 10 | none found |
| 11 | Todd M. Allen, Harvard University | animal | 1 of 1 | 0 | 0 | 11 | none found |
| 12 | Darrell J. Irvine, Harvard University | animal | 1 of 1 | 0 | 0 | 12 | none found |
| 13 | Christopher Austin Klebanoff, Cornell University | animal | 1 of 1 | 0 | 0 | 13 | none found |
| 14 | Shahab Asgharzadeh, University of Southern California | animal | 1 of 1 | 0 | 0 | 14 | none found |
Claims and their evidence
Donald M. O’Rourke, University of Pennsylvania
- C10 Patient-derived glioblastoma organoids treated in parallel with autologous EGFR-IL13Rα2 CAR-T cell products showed cytolysis that correlated with CAR-T engraftment in patient cerebrospinal fluid. Reported effect: Degree of cytolysis significantly correlated with CSF CAR-T engraftment for all six patients; cytokine kinetics mirrored CSF levels over time.
- human; verified against its paper; no independent support found in this corpus; source: TMOD-02. PATIENT-DERIVED GLIOBLASTOMA ORGANOIDS AS REAL-TIME AVATARS FOR ASSESSING RESPONSES TO CLINICAL CAR-T CELL THERAPY (2024-11-01, P25)
- Own paper:
- claim: "showed cytolysis that correlated with CAR-T engraftment in patient cerebrospinal fluid" / paper: "the degree of cytolysis ex vivo significantly correlated with CAR-T cell engraftment detected in patients’ cerebrospinal fluid (CSF) for all six patients." — TMOD-02. PATIENT-DERIVED GLIOBLASTOMA ORGANOIDS AS REAL-TIME AVATARS FOR ASSESSING RESPONSES TO CLINICAL CAR-T CELL THERAPY (2024-11-01, P25). Paper reports the same correlation in all six patients. [R4020]
- C11 A 4-1BB-costimulated CAR fusing mAb 806 targets EGFR amplification, EGFRvIII and EGFR-ECD mutations, with superior in vivo antitumor activity versus 2173 CAR T cells. Reported effect: Not quantified in abstract; 806 CAR T cells described as showing superior in vivo antitumor activity compared with 2173 CAR T cells.
- in vitro; verified against its paper; no independent support found in this corpus; source: High-Affinity Chimeric Antigen Receptor With Cross-Reactive scFv to Clinically Relevant EGFR Oncogenic Isoforms (2021-09-10, P27)
- Own paper:
- claim: "superior in vivo antitumor activity versus 2173 CAR T cells" / paper: "They also exhibited superior antitumor activity in vivo when compared to 2173 CAR T cells." — High-Affinity Chimeric Antigen Receptor With Cross-Reactive scFv to Clinically Relevant EGFR Oncogenic Isoforms (2021-09-10, P27). Paper reports the same 4-1BB mAb 806 CAR and superior in vivo activity versus 2173. [R4021]
Terry J. Fry, University of Colorado Anschutz
- C07 CD28-based CD33-directed CAR T cells consistently inhibited leukemia proliferation more robustly than 4-1BB-based constructs; lintuzumab-CD28/CD3ζ was selected for clinical translation.
- animal; verified against its paper; no independent support found in this corpus; source: Systematic preclinical evaluation of CD33-directed chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia defines optimized construct design (2021-09-01, P13)
- Own paper:
- claim: "lintuzumab-CD28/CD3ζ was selected for clinical translation" / paper: "CD28-based CD33CARTs consistently induced more robust inhibition of leukemia proliferation in AML cell line and PDX models than did 4-1BB-based CD33CARTs." — Systematic preclinical evaluation of CD33-directed chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia defines optimized construct design (2021-09-01, P13). Paper reports CD28-based CD33 CARTs more robust than 4-1BB-based and lintuzumab-CD28/CD3ζ selected for translation. [R4017]
- C12 Boosting CD22-CAR binding affinity without shortening the flexible linker maintains maximal CAR function against CD22-low and wild-type leukemia.
- animal; verified against its paper; no independent support found in this corpus; source: Rational redesign of antigen binding domain improves in vivo efficacy of the CD22-CAR (2025-12-24, P31)
- Own paper:
- claim: "Boosting CD22-CAR binding affinity without shortening the flexible linker maintains maximal CAR function" / paper: "maximal CAR function in the settings CD22 Lo and WT leukemia is maintained by boosting binding affinity without shortening flexible linker to induce tonic signaling" — Rational redesign of antigen binding domain improves in vivo efficacy of the CD22-CAR (2025-12-24, P31). Paper states the same result for CD22-low and wild-type leukemia. [R4022]
- C24 T-bet overexpression in CAR T cells reduces IL-4 expression, increases polyfunctional Th1 cytokine production, and enhances 4-1BB CAR T activity against low-antigen leukemia without impairing persistence.
- animal; verified against its paper; no independent support found in this corpus; source: T-bet overexpression enhances CAR T cell effector functions and antigen sensitivity (2025-04-01, P18)
- Own paper:
- claim: "increases polyfunctional Th1 cytokine production, and enhances 4-1BB CAR T activity against low-antigen leukemia without impairing persistence" / paper: "an increase in polyfunctional Th1 cytokine production and enhances 4-1BB CAR T cell activity against cancers expressing low levels of target antigen without promoting a loss in functional CAR T cell persistence." — T-bet overexpression enhances CAR T cell effector functions and antigen sensitivity (2025-04-01, P18). Paper reports reduced IL-4, increased Th1 cytokines, and enhanced 4-1BB CAR T activity against low antigen without persistence loss. [R4034]
Wayne Anthony Marasco, Harvard University
- C13 BBζ CD4/CD8 mixture (CAR4/8) CAIX-targeted CAR-T cells gave superior efficacy over 28ζ and 28BBζ constructs, with complete tumor remission in a ccRCC model. Reported effect: Mice given a single dose of BBζ CAR4/8 showed complete tumor remission and remained tumor-free 72 days after infusion.
- animal; verified against its paper; no independent support found in this corpus; source: Anti-CAIX BBζ CAR4/8 T cells exhibit superior efficacy in a ccRCC mouse model (2021-12-31, P17)
- Own paper:
- claim: "showed complete tumor remission and remained tumor-free 72 days after infusion" / paper: "The mice treated with a single dose of BBζ CD4/CD8 mixture (CAR4/8) showed complete tumor remission and remained tumor-free 72 days after CAR-T cells infusion." — Anti-CAIX BBζ CAR4/8 T cells exhibit superior efficacy in a ccRCC mouse model (2021-12-31, P17). Paper reports the same BBζ superiority over 28ζ and 28BBζ and complete remission at 72 days. [R4023]
- C21 A low-affinity/high-avidity anti-CAIX CAR (G9) mitigates on-target off-tumor toxicity while retaining efficacy against CAIX-high tumors, unlike high-affinity G250. Reported effect: G9 CAR-T showed a wider therapeutic window than G250 and enhanced tumor control in the orthotopic model; no numerical effect sizes stated.
- animal; verified against its paper; no independent support found in this corpus; source: Affinity fine-tuning anti-CAIX CAR-T cells mitigate on-target off-tumor side effects (2024-03-16, P42)
- Own paper:
- claim: "low-affinity/high-avidity anti-CAIX CAR (G9) mitigates on-target off-tumor toxicity" / paper: "low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250" — Affinity fine-tuning anti-CAIX CAR-T cells mitigate on-target off-tumor side effects (2024-03-16, P42). Paper reports the same wider window versus G250 and enhanced tumor control in the orthotopic model. [R4031]
Xianxin Hua, University of Pennsylvania
- C16 Third-generation dual nanobody-redirected CD13/TIM-3 bispecific CAR T cells (nbiCARTs) showed strong antitumor activity against CD13/TIM3-positive leukemic cells and had little toxicity to human HSCs.
- animal; verified against its paper; no independent support found in this corpus; source: Dual nanobody-redirected and Bi-specific CD13/TIM3 CAR T cells eliminate AML xenografts without toxicity to human HSCs (2025-02-20, P03)
- Own paper:
- claim: "showed strong antitumor activity against CD13/TIM3-positive leukemic cells and had little toxicity to human HSCs" / paper: "Importantly, the 3rd generation of nbiCARTs had little toxicity to human bone marrow-derived colony forming progenitors ex vivo and the human HSCs in mice with a humanized immune system." — Dual nanobody-redirected and Bi-specific CD13/TIM3 CAR T cells eliminate AML xenografts without toxicity to human HSCs (2025-02-20, P03). Paper reports the same third-generation nbiCART antitumor activity and low HSC toxicity. [R4026]
- C18 A nanobody VHHB30 binding the N-terminal nonglycosylated domain of CEA, used in CAR T cells, eliminates colorectal and gastric tumor xenografts in mice.
- animal; verified against its paper; no independent support found in this corpus; source: Nanobody-Directed CEA-Targeting CAR T Cells Eliminate Gastrointestinal Cancer Xenografts (2025-05-29, P48)
- Own paper:
- claim: "eliminates colorectal and gastric tumor xenografts in mice" / paper: "in vivo studies demonstrated that the CEACAR T cells eradicated various colorectal and gastric tumor xenografts in preclinical mouse models" — Nanobody-Directed CEA-Targeting CAR T Cells Eliminate Gastrointestinal Cancer Xenografts (2025-05-29, P48). Paper reports VHHB30 CEA nanobody CAR T cells eradicating colorectal and gastric xenografts. [R4028]
Nicola J. Mason, University of Pennsylvania
- C15 A fully canine anti-cPD-1 IgGD antibody, derived from canine scFvs, blocks cPD-1:cPD-L1 interaction, reverses its effect on CAR T function, and shows favorable pharmacokinetics without toxicity.
- animal; verified against its paper; no independent support found in this corpus; source: Development and pharmacokinetic assessment of a fully canine anti-PD-1 monoclonal antibody for comparative translational research in dogs with spontaneous tumors (2023-12-04, P09)
- Own paper:
- claim: "blocks cPD-1:cPD-L1 interaction, reverses its effect on CAR T function, and shows favorable pharmacokinetics without toxicity" / paper: "In vivo administration showed no toxicity and revealed favorable pharmacokinetics for a reasonable dosing schedule." — Development and pharmacokinetic assessment of a fully canine anti-PD-1 monoclonal antibody for comparative translational research in dogs with spontaneous tumors (2023-12-04, P09). Paper reports the fully canine IgGD reversing the inhibitory effect on CAR T function with no toxicity and favorable pharmacokinetics. [R4025]
- C17 A PD-1/CD28 chimeric switch receptor expressed in canine CAR-T cells enhances function against PD-L1+ targets and preserves central memory phenotype, depending on active CSR signaling.
- in vitro; verified against its paper; no independent support found in this corpus; source: Validation of a PD-1/CD28 chimeric switch receptor to augment CAR-T function in dogs with spontaneous B cell lymphoma (2024-08-30, P22)
- Own paper:
- claim: "enhances function against PD-L1+ targets and preserves central memory phenotype" / paper: "expression of a PD-1/CD28 CSR in canine CAR-T cells results in enhanced function against PD-L1 + targets and preserves central memory phenotype." — Validation of a PD-1/CD28 chimeric switch receptor to augment CAR-T function in dogs with spontaneous B cell lymphoma (2024-08-30, P22). Paper states the same effects and dependence on active CSR signaling. [R4027]
Hideho Okada, University of California, San Francisco
- C06 A novel transgenic mouse strain expressing a fully murinized EGFRvIII-CAR on T-cells provides consistent CAR-T cells for syngeneic glioblastoma studies, and CART plus anti-EP4 compound ONO-AE3-208 gave long-term survival in some mice.
- animal; verified against its paper; no independent support found in this corpus; source: Novel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice (2021-08-02, P06)
- Own paper:
- claim: "CART plus anti-EP4 compound ONO-AE3-208 gave long-term survival in some mice" / paper: "The addition of ONO-AE3-208 resulted in long-term survival in a fraction of CART-treated mice" — Novel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice (2021-08-02, P06). Paper reports the transgenic syngeneic model and long-term survival in a fraction of mice. [R4016]
- C03 Brevican-primed synNotch-α-B7H3/IL13Ra2 CAR T cells (B-SYNC) completely killed D283 medulloblastoma cells only when primed by BCAN-expressing K562 cells. Reported effect: B-SYNC T cells killed D425 cells at a 17% faster rate than constitutive α-B7H3/IL13Ra2 CAR T cells on brevican-coated plates.
- in vitro; verified against its paper; no independent support found in this corpus; source: IMMU-03. Engineering novel synNotch-CAR T cells to precisely and effectively target medulloblastoma (2025-08-01, P39)
- Own paper:
- claim: "completely killed D283 medulloblastoma cells only when primed by BCAN-expressing K562 cells" / paper: "B-SYNC T cells completely killed the medulloblastoma cell line, D283, only when primed by K562 cells expressing BCAN." — IMMU-03. Engineering novel synNotch-CAR T cells to precisely and effectively target medulloblastoma (2025-08-01, P39). Paper states the same priming-dependent killing and the 17% faster rate on brevican-coated plates. [R4013]
Stanley R. Riddell, University of Washington
- C14 A novel synthetic chimeric TCR (ChTCR), including bispecific Bi-ChTCR designs, exhibits superior antigen sensitivity and eliminates tumors with heterogeneous antigen expression better than optimized bispecific CARs.
- animal; verified against its paper; no independent support found in this corpus; source: Design of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy (2025-03-17, P26)
- Own paper:
- claim: "exhibits superior antigen sensitivity and eliminates tumors with heterogeneous antigen expression better than optimized bispecific CARs" / paper: "T cells expressing Bi-ChTCRs more effectively eliminated tumors with heterogeneous antigen expression in vivo compared to T cells expressing optimized bispecific CARs." — Design of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy (2025-03-17, P26). Paper states the same ChTCR superiority. [R4024]
- C22 CARs with embedded CD3ε or GRB2 domains, engaging CD3ε and LAT more effectively, enhance T cell activation at low antigen density and improve in vivo efficacy.
- animal; verified against its paper; no independent support found in this corpus; source: Comparative analysis of TCR and CAR signaling informs CAR designs with superior antigen sensitivity and in vivo function (2021-08-24, P19)
- Own paper:
- claim: "CARs with embedded CD3ε or GRB2 domains, engaging CD3ε and LAT more effectively, enhance T cell activation at low antigen density" / paper: "better engage CD3ε and LAT using embedded CD3ε or GRB2 domains resulted in enhanced T cell activation in vitro in settings of a low density of antigen" — Comparative analysis of TCR and CAR signaling informs CAR designs with superior antigen sensitivity and in vivo function (2021-08-24, P19). Paper reports the same design, low-antigen activation, and improved in vivo efficacy. [R4032]
Anjie Zhen, University of California, Los Angeles
- C02 Low-dose rapamycin combined with HSC-derived anti-HIV CAR-T cells reduced chronic inflammation, prevented CAR-T exhaustion, delayed viral rebound after ART withdrawal, and reduced HIV reservoir in humanized mice.
- animal; verified against its paper; no independent support found in this corpus; source: Rapamycin enhances CAR-T control of HIV replication and reservoir elimination in vivo (2025-02-11, P41)
- Own paper:
- claim: "delayed viral rebound after ART withdrawal, and reduced HIV reservoir in humanized mice" / paper: "Mice treated with CAR-HSCs and rapamycin had delayed viral rebound after ART and reduced HIV reservoir compared with those treated with CAR-HSCs alone." — Rapamycin enhances CAR-T control of HIV replication and reservoir elimination in vivo (2025-02-11, P41). Paper reports the same rapamycin plus CAR-HSC outcomes in humanized mice. [R4012]
- C23 Low-dose rapamycin enhanced anti-HIV CAR-T cell function, reducing exhaustion, improving viral control, delaying rebound after ART withdrawal and lowering HIV reservoir in CAR-HSC humanized mice.
- animal; not verified against its paper; no independent support found in this corpus; source: Rapamycin Enhances CAR-T Control of HIV Replication and Reservoir Elimination in vivo 3825 (2025-11-01, P08)
- Same-group support:
- claim: "delaying rebound after ART withdrawal and lowering HIV reservoir in CAR-HSC humanized mice" / paper: "In vivo treatment with low-dose rapamycin in HIV-infected, CAR-HSC mice decreased chronic inflammation, prevented exhaustion of CAR-T cells, and improved CAR-T control of viral replication." — Rapamycin enhances CAR-T control of HIV replication and reservoir elimination in vivo (2025-02-11, P41). Paper reports the same low-dose rapamycin effects in CAR-HSC humanized mice including delayed rebound and reduced reservoir. [R4033]
Soheil Meshinchi, University of Washington
- C04 FH FOLR1-CART, a FOLR1-specific CAR T-cell product, shows robust in vitro activation, potent cytotoxicity, and antitumor activity in localized and metastatic osteosarcoma xenografts. Reported effect: Complete tumor eradication reported in localized and metastatic in vivo cell-derived and patient-derived xenograft models; no numeric values stated.
- animal; not verified against its paper; no independent support found in this corpus; source: Preclinical Evaluation of Folate Receptor-α Chimeric Antigen Receptor T Cells Exhibits Highly Efficient Antitumor Activity against Osteosarcoma (2025-09-01, P15)
- C19 MSLN-directed CAR T cells (41-BB and CD3Zeta domains, SS1P-derived scFv) eliminate MSLN-positive AML cells and spare normal HSPCs; ADAM17 inhibition improves CAR T function.
- animal; verified against its paper; no independent support found in this corpus; source: Therapeutic Targeting of Mesothelin with Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia (2021-08-11, P43)
- Own paper:
- claim: "eliminate MSLN-positive AML cells and spare normal HSPCs; ADAM17 inhibition improves CAR T function" / paper: "we show that CAR T-cell functionality can be improved by inhibition of the ADAM17 metalloprotease that promotes shedding of MSLN." — Therapeutic Targeting of Mesothelin with Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia (2021-08-11, P43). Paper reports the same SS1P-derived MSLN CAR eliminating AML cells, sparing HSPCs, and ADAM17 inhibition improving function. [R4029]
Samuel K. Lai, University of North Carolina at Chapel Hill
- C05 A bispecific binder redirected lentiviral vector expressing a mutant Sindbis envelope generates CD19-specific CAR-T cells in vivo that control a pre-established xenograft B cell tumor.
- animal; verified against its paper; no independent support found in this corpus; source: Bispecific binder redirected lentiviral vector enables in vivo engineering of CAR-T cells (2021-09-01, P50)
- Own paper:
- claim: "generates CD19-specific CAR-T cells in vivo that control a pre-established xenograft B cell tumor" / paper: "generates CD19-specific CAR-T cells that markedly control the growth of an aggressive pre-established xenograft B cell tumor." — Bispecific binder redirected lentiviral vector enables in vivo engineering of CAR-T cells (2021-09-01, P50). Paper reports the same in vivo CAR-T generation and tumor control. [R4015]
Todd M. Allen, Harvard University
- C08 Immunosuppressants rapamycin and tacrolimus mitigate allorejection of HLA-mismatched CAR-T cells, and FKBP1A knockout confers CAR-T cells functional resistance to these drugs while preserving tumor control. Reported effect: Immunosuppressant treatment extended persistence of HLA-mismatched CAR-T cells to that of syngeneic CAR-T cells; no numeric values stated in abstract.
- animal; verified against its paper; no independent support found in this corpus; source: Immunosuppressant therapy averts rejection of allogeneic FKBP1A-disrupted CAR-T cells (2024-09-01, P33)
- Own paper:
- claim: "rapamycin and tacrolimus mitigate allorejection of HLA-mismatched CAR-T cells" / paper: "the immunosuppressants rapamycin and tacrolimus effectively mitigate allorejection of HLA-mismatched CAR-T cells in immunocompetent humanized mice" — Immunosuppressant therapy averts rejection of allogeneic FKBP1A-disrupted CAR-T cells (2024-09-01, P33). Paper states the same mitigation, persistence like syngeneic cells, and FKBP1A KO resistance. [R4018]
Darrell J. Irvine, Harvard University
- C01 Yeast-display-derived peptide mimotopes, affinity matured by directed evolution, can serve as surrogate ligands in CAR-T vaccines that expand CD19 CAR-T cells in vivo. Reported effect: Marked expansion of CAR-T cells and enhanced control of leukemia progression; no numerical effect sizes stated in abstract.
- animal; verified against its paper; no independent support found in this corpus; source: Directed evolution-based discovery of ligands for in vivo restimulation of chimeric antigen receptor T cells (2025-08-25, P20)
- Own paper:
- claim: "Yeast-display-derived peptide mimotopes, affinity matured by directed evolution" / paper: "we employed yeast surface display to identify peptide binders to soluble IgG versions of FMC63, which were subsequently affinity matured by directed evolution." — Directed evolution-based discovery of ligands for in vivo restimulation of chimeric antigen receptor T cells (2025-08-25, P20). Paper reports yeast-display mimotopes affinity matured by directed evolution used in CAR-T vaccines. [R4011]
Christopher Austin Klebanoff, Cornell University
- C20 Disrupting FAS death receptor signaling via a dominant-negative FAS receptor (∆FAS) enhances persistence and antitumor efficacy of CAR-T and CAR-NK cells, with FAS-L acting as an auto-regulatory survival circuit. Reported effect: Bone marrow tEGFR/tLNGFR ratio 11.6 in FASLG WT vs 1.7 in FASLG KO CAR-T cells; FASLG KO showed no survival change vs WT (p=0.5634); ∆FAS improved antitumor efficacy (p<0.05).
- animal; verified against its paper; no independent support found in this corpus; source: Enhancing the Persistence and Anti-Tumor Efficacy of CAR-T and CAR-NK Cells through Genetic Disruption of Death Receptors (2025-02-01, P02)
- Own paper:
- claim: "Bone marrow tEGFR/tLNGFR ratio 11.6 in FASLG WT vs 1.7 in FASLG KO CAR-T cells" / paper: "1.7 in FASLG WT vs KO CAR-T cells in bone marrow" — Enhancing the Persistence and Anti-Tumor Efficacy of CAR-T and CAR-NK Cells through Genetic Disruption of Death Receptors (2025-02-01, P02). Paper reports the same bone marrow ratios of 11.6 and 1.7 for FASLG WT versus KO CAR-T cells. [R4087]
Shahab Asgharzadeh, University of Southern California
- C09 B7H3 CAR T-cells secreting GD2-CD3 BiTEs recruit bystander T-cells and show superior survival versus B7H3 CAR T-cells in a pediatric high-grade glioma murine model. Reported effect: GD2-CD3.B7H3 BiTE-secreting CAR T-cells showed superior survival versus B7H3 CAR T-cells; no numeric values stated.
- animal; verified against its paper; no independent support found in this corpus; source: IMMU-14. Secretion of GD2-CD3 BiTEs from B7H3 CAR T-Cells Enhances their Anti-Tumor Activity in Pediatric High-Grade Gliomas (2025-08-01, P30)
- Own paper:
- claim: "show superior survival versus B7H3 CAR T-cells in a pediatric high-grade glioma murine model" / paper: "GD2-CD3.B7H3 BiTE-secreting CAR T-cells demonstrated superior survival in the pHGG murine model compared to B7H3 CAR T-cells." — IMMU-14. Secretion of GD2-CD3 BiTEs from B7H3 CAR T-Cells Enhances their Anti-Tumor Activity in Pediatric High-Grade Gliomas (2025-08-01, P30). Paper reports the same superior survival and bystander T-cell recruitment. [R4019]
Framed read (unvalidated: one model's synthesis of the records above)
Claim that carries the most weight: C05. C05 is the only claim on the sheet in which the CAR-T cells are generated inside the animal by a vector, which is what in vivo CAR-T means; most other claims concern engineered cells or receptor design. If it does not stand, the sheet has little left that bears on the topic itself, and it rests on a single animal-tier record from the claim's own paper.
What would have to hold:
- The vector-generated CAR-T result in a pre-established xenograft (R4015) has to hold beyond the originating lab; no independent paper in this pack addresses it.
- Control of tumor growth has to reflect CAR-T cells made in vivo rather than ex vivo manipulation; R4015 quotes the result but no record covers dosing, durability or off-target transduction.
- The in vivo expansion route in C01 (R4011) has to be real and not tied to one reagent; the record comes from the claim's own paper and no independent paper in this pack addresses it.
- Safety of the delivery vector (biodistribution, unintended cell types transduced) has to be acceptable; no record covers it.
- A mouse xenograft result has to carry to human tissue; only C10 (R4020) is human-tier, and it concerns an ex vivo organoid correlation, not vector delivery.
Questions a data room would have to answer:
- (C05) In the pre-established xenograft study, what were the vector dose, route and number of animals per arm, how long was tumor control sustained, and was transduction of non-T cells measured?
- (C01) Does the mimotope-based expansion work with CAR constructs other than the one used, and what happens to CAR-T persistence and cytokine release after repeated vaccination?
- (C07) The record for this claim quotes the CD28 versus 4-1BB comparison but not the selection for clinical translation: what data room evidence supports that choice, and is any clinical-grade manufacturing or regulatory filing in hand?
- (C20) The record quotes only the knockout bone marrow ratio; what are the raw ratios and animal counts for the wild-type arm, and why did FASLG knockout show no survival change while the dominant-negative receptor did improve efficacy?
- (C15) The record covers toxicity and pharmacokinetics only: what data show the canine antibody reverses the inhibitory effect on CAR T function, and is a path from canine to human therapeutics planned?
- (C03) The faster-killing figure sits outside the quoted record text: what is the underlying assay, and does priming-dependent killing survive in an in vivo medulloblastoma model rather than coated plates?
- (C23) This record's paper is the same one as for the rapamycin claim C02 and is not independent: how many humanized-mouse cohorts were run, and is there any data on rapamycin interaction with CAR-HSC engraftment?
- (C08) Immunosuppressant treatment mitigated allorejection in humanized mice: what are the drug exposure levels, and does the FKBP1A knockout preserve tumor control in a setting with an intact human-like immune system over long follow-up?
Cannot say:
- Whether any result here is reproduced by another lab: every record is marked not independent and comes from the claim's own paper or the same paper as a sibling claim.
- How large any effect is: most records quote qualitative statements, and no record gives effect sizes for the in vivo generation claims.
- Whether any approach is safe or manufacturable in humans: the records are mostly animal and in vitro tier, with a single human-tier claim concerning organoids.
- Whether the in vivo CAR-T approach beats ex vivo CAR-T products: no record compares the two.
- Anything about the labs' commercial position, IP, funding or team, since the records contain only claim and paper quotes.
What was not shown
- Claims with no checked record: C04.
- Records proposed: 25; refused by code (a quote not found, or a number of the reader's own): 2; removed by the checker: 0.
- Papers without an abstract, not read: 0.
Run record
- run: sci-136c24b4df; reader arm: B1R; spec: sci-0.1; rank rule: scirank-v1
- reader prompt sha256: c04daba6743bf488eaeb3427cec02860a257d2c06ef9f58cf307195206620e03; model: claude-sonnet-5-5, medium effort
- extraction: claude-haiku-5-5, prompt extract_v0.3; no human has verified it