Science brief: a reading aid, unvalidated by any person. Not a prediction and not advice. Public data only.

Science brief: antibody-drug conjugate

As of 2025-12-31. Topic mode. Literature: antibody-drug conjugate. 51 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

Claims and their evidence

Jonathan Wade Goldman, University of California, Los Angeles

• C06 Temab-A combined with budigalimab will be evaluated for safety, ORR and phase 3 dose selection in advanced NSQ EGFR wildtype NSCLC with no prior systemic therapy for advanced disease.
  • human, randomized (by rule); verified against its paper; no independent support found in this corpus; source: Phase 1b/2 study evaluating telisotuzumab adizutecan (ABBV-400; Temab-A) in combination with budigalimab in patients (pts) with advanced non-squamous (NSQ) non-small cell lung cancer (NSCLC) with no prior treatment for advanced disease and no actionable genomic alterations. (2025-05-28, P33)
  • Own paper:
    • claim: "Temab-A combined with budigalimab will be evaluated for safety, ORR and phase 3 dose selection" / paper: "Primary objectives are to evaluate safety and tolerability, assess efficacy as measured by ORR by blinded independent central review, and select the recommended phase 3 dose" — Phase 1b/2 study evaluating telisotuzumab adizutecan (ABBV-400; Temab-A) in combination with budigalimab in patients (pts) with advanced non-squamous (NSQ) non-small cell lung cancer (NSCLC) with no prior treatment for advanced disease and no actionable genomic alterations. (2025-05-28, P33). Trial design paper states the same objectives for Temab-A plus budigalimab in NSQ NSCLC. [R4040]
• C15 Telisotuzumab vedotin plus osimertinib showed promising activity and manageable safety in c-Met protein-overexpressing, EGFR-mutated non-squamous NSCLC after progression on osimertinib. Reported effect: ORR 50.0% (DOR not reached); median PFS 7.4 months (95% CI 5.4 months-not reached) after median follow-up of 7.4 months, n=38.
  • human; verified against its paper; no independent support found in this corpus; source: Results from a phase Ib study of telisotuzumab vedotin in combination with osimertinib in patients with c-Met protein-overexpressing, EGFR-mutated locally advanced/metastatic non-small-cell lung cancer (NSCLC) after progression on prior osimertinib (2025-01-11, P44)
  • Own paper:
    • claim: "ORR 50.0% (DOR not reached); median PFS 7.4 months" / paper: "After a median follow-up of 7.4 months, the ORR was 50.0% per independent central review (ICR) (DOR not reached)" — Results from a phase Ib study of telisotuzumab vedotin in combination with osimertinib in patients with c-Met protein-overexpressing, EGFR-mutated locally advanced/metastatic non-small-cell lung cancer (NSCLC) after progression on prior osimertinib (2025-01-11, P44). Same combination, population, ORR, PFS and n=38. [R4049]

Stephen E. F. Spurgeon, Oregon Health & Science University

• C20 Zilovertamab vedotin, an anti-ROR1 antibody-drug conjugate, showed no unexpected toxicities and antitumor activity in heavily pretreated lymphoid cancer patients. Reported effect: Objective responses: MCL 47% (4 partial, 3 complete); DLBCL 60% (1 partial, 2 complete); recommended dose 2.5 mg/kg every 3 weeks.
  • human; verified against its paper; no independent support found in this corpus; source: Zilovertamab Vedotin Targeting of ROR1 as Therapy for Lymphoid Cancers (2021-12-22, P35)
  • Own paper:
    • claim: "showed no unexpected toxicities and antitumor activity in heavily pretreated lymphoid cancer patients" / paper: "ZV induced objective tumor responses in 7 of 15 patients with MCL (47%; 4 partial and 3 complete) and in 3 of 5 patients with DLBCL (60%; 1 partial and 2 complete)" — Zilovertamab Vedotin Targeting of ROR1 as Therapy for Lymphoid Cancers (2021-12-22, P35). Same trial, response rates and 2.5 mg/kg every 3 weeks dose. [R4054]
• C22 Zilovertamab vedotin (MK-2140), an anti-ROR1 antibody-drug conjugate, showed a tolerable safety profile and promising antitumor activity in relapsed/refractory NHL. Reported effect: MTD 2.5 mg/kg; ORR 36.6% (15/41, 95% CI 22.1%-53.1%) in NHL; DLBCL ORR 38.5%; MCL ORR 52.9%; grade ≥3 treatment-related AEs 47.1%.
  • human; verified against its paper; no independent support found in this corpus; source: P1231: ZILOVERTAMAB VEDOTIN (MK-2140) FOR THE TREATMENT OF NON-HODGKIN LYMPHOMA: THE PHASE 1 DOSE ESCALATION AND COHORT EXPANSION WAVELINE-001 STUDY OF AN ANTI-ROR1 ANTIBODY-DRUG CONJUGATE (2022-06-01, P27)
  • Own paper:
    • claim: "ORR 36.6% (15/41, 95% CI 22.1%-53.1%) in NHL" / paper: "ORR was 36.6% (15/41 [95% CI, 22.1%-53.1%]; 5 CR; 10 PR) among all pts with NHL." — P1231: ZILOVERTAMAB VEDOTIN (MK-2140) FOR THE TREATMENT OF NON-HODGKIN LYMPHOMA: THE PHASE 1 DOSE ESCALATION AND COHORT EXPANSION WAVELINE-001 STUDY OF AN ANTI-ROR1 ANTIBODY-DRUG CONJUGATE (2022-06-01, P27). Same WAVELINE-001 study with matching MTD, ORR, subtype ORRs and grade 3 or higher AE rate. [R4056]

Karen L. Kelly, University of California, Davis

• C02 Telisotuzumab vedotin plus nivolumab was well tolerated in c-Met-positive advanced NSCLC patients, with limited antitumor activity. Reported effect: ORR 7.4% with two confirmed partial responses; median PFS 7.2 months (PD-L1+ 7.2 mo; PD-L1- 4.5 mo); 37 treated, 27 efficacy population.
  • human; verified against its paper; no independent support found in this corpus; source: A Phase 1b Study of Telisotuzumab Vedotin in Combination With Nivolumab in Patients With NSCLC (2021-12-04, P30)
  • Own paper:
    • claim: "was well tolerated in c-Met-positive advanced NSCLC patients, with limited antitumor activity" / paper: "Combination therapy with Teliso-V plus nivolumab was well tolerated in patients with c-Met+ NSCLC with limited antitumor activity." — A Phase 1b Study of Telisotuzumab Vedotin in Combination With Nivolumab in Patients With NSCLC (2021-12-04, P30). Same combination, tolerability and limited activity conclusion, with matching ORR and PFS numbers. [R4036]
• C17 Telisotuzumab vedotin monotherapy was tolerated and showed antitumor activity in c-Met+ NSCLC; 1.9 mg/kg once every 2 weeks and 2.7 mg/kg once every 3 weeks were selected for further development. Reported effect: Objective responses in 9 (23%) of 40 c-Met+ patients, median DOR 8.7 months, median PFS 5.2 months.
  • human; verified against its paper; no independent support found in this corpus; source: Phase I Study of 2- or 3-Week Dosing of Telisotuzumab Vedotin, an Antibody–Drug Conjugate Targeting c-Met, Monotherapy in Patients with Advanced Non–Small Cell Lung Carcinoma (2021-08-23, P39)
  • Own paper:
    • claim: "1.9 mg/kg once every 2 weeks and 2.7 mg/kg once every 3 weeks were selected for further development" / paper: "Of those, 9 (23%) had objective responses with median duration of response of 8.7 months; median progression-free survival was 5.2 months." — Phase I Study of 2- or 3-Week Dosing of Telisotuzumab Vedotin, an Antibody–Drug Conjugate Targeting c-Met, Monotherapy in Patients with Advanced Non–Small Cell Lung Carcinoma (2021-08-23, P39). Same monotherapy study, doses selected, 9 responders of 40 and DOR and PFS values. [R4051]

Carmelo Carlo‐Stella, Harvard University

• C01 Loncastuximab tesirine 60 µg/kg plus ibrutinib 560 mg showed encouraging antitumor activity with manageable toxicity in relapsed/refractory DLBCL or MCL. Reported effect: ORR 63.9% overall (36.1% complete, 27.8% partial response); 58.6% in all DLBCL and 85.7% in MCL; TEAEs 100%, grade ≥3 TEAEs 64.9%.
  • human; verified against its paper; no independent support found in this corpus; source: CLINICAL ACTIVITY OF LONCASTUXIMAB TESIRINE PLUS IBRUTINIB IN NON‐HODGKIN LYMPHOMA: UPDATED LOTIS 3 PHASE 1 RESULTS (2021-06-01, P02)
  • Own paper:
    • claim: "Loncastuximab tesirine 60 µg/kg plus ibrutinib 560 mg showed encouraging antitumor activity with manageable toxicity" / paper: "Results indicate that Lonca 60 µg/kg plus ibrutinib 560 mg has encouraging antitumor activity, with manageable toxicity in R/R DLBCL or R/R MCL." — CLINICAL ACTIVITY OF LONCASTUXIMAB TESIRINE PLUS IBRUTINIB IN NON‐HODGKIN LYMPHOMA: UPDATED LOTIS 3 PHASE 1 RESULTS (2021-06-01, P02). Same drugs, doses, and conclusion; ORR figures also match the abstract. [R4035]
• C11 Camidanlumab tesirine (Cami), an anti-CD25 antibody-drug conjugate, showed efficacy in heavily pretreated relapsed/refractory classic Hodgkin lymphoma, but safety issues overshadowed benefit. Reported effect: ORR 70.1% (95% CI 60.9-78.2); CRR 33.3%; median PFS 9.13 months; 28.2% discontinued for treatment-emergent adverse events.
  • human; verified against its paper; no independent support found in this corpus; source: Camidanlumab tesirine for relapsed or refractory classic Hodgkin lymphoma: a phase 2 study (2025-08-14, P29)
  • Own paper:
    • claim: "showed efficacy in heavily pretreated relapsed/refractory classic Hodgkin lymphoma, but safety issues overshadowed benefit" / paper: "The ORR was 70.1% (95% confidence interval [CI], 60.9-78.2), with a CRR of 33.3% (95% CI, 24.9-42.6)." — Camidanlumab tesirine for relapsed or refractory classic Hodgkin lymphoma: a phase 2 study (2025-08-14, P29). Same trial, ORR, CRR, PFS and discontinuation figures with the same efficacy-versus-safety conclusion. [R4045]

Greg M. Thurber, University of Michigan

• C04 IKS04, a CanAg-targeting ADC with a pyrrolobenzodiazepine prodrug payload, shows enhanced efficacy when coadministered with unconjugated Isumab04 antibody. Reported effect: Isumab04 coadministration improved tumor distribution and increased in vivo efficacy; greater efficacy with higher antibody doses until tumor saturation; no numeric values stated.
  • animal; verified against its paper; no independent support found in this corpus; source: IKS04, a CanAg-Targeting Antibody–Drug Conjugate with Pyrrolobenzodiazepine, Shows Enhanced Efficacy with Unconjugated Antibody Coadministration in Animal Models (2025-10-07, P49)
  • Own paper:
    • claim: "shows enhanced efficacy when coadministered with unconjugated Isumab04 antibody" / paper: "increasing doses of unconjugated antibody resulted in greater efficacy until apparent tumor saturation was reached." — IKS04, a CanAg-Targeting Antibody–Drug Conjugate with Pyrrolobenzodiazepine, Shows Enhanced Efficacy with Unconjugated Antibody Coadministration in Animal Models (2025-10-07, P49). Paper reports enhanced efficacy with Isumab04 coadministration and dose-dependent gains until saturation. [R4038]
• C07 High-Avidity, Low-Affinity (HALA) antibodies co-administered with HER2 antibody-drug conjugates auto-tune cellular ADC delivery to match local target expression, improving efficacy across expression levels.
  • animal; verified against its paper; no independent support found in this corpus; source: In Vivo Auto-tuning of Antibody–Drug Conjugate Delivery to Maximize Efficacy Using High-Avidity, Low-Affinity Antibodies (2025-12-30, P31)
  • Own paper:
    • claim: "High-Avidity, Low-Affinity (HALA) antibodies co-administered with HER2 antibody-drug conjugates auto-tune cellular ADC delivery" / paper: "This translated to greater ADC efficacy in immunodeficient mouse models across a range of HER2 expression levels." — In Vivo Auto-tuning of Antibody–Drug Conjugate Delivery to Maximize Efficacy Using High-Avidity, Low-Affinity Antibodies (2025-12-30, P31). Paper reports HALA antibodies tune ADC delivery and improve efficacy across HER2 expression levels. [R4041]

Donald W. Kufe, Harvard University

• C24 An anti-MUC1-C antibody-drug conjugate is highly effective against MRTX1133-resistant PDAC KRAS G12D models, and MUC1-C drives resistance to KRAS G12D inhibition via IFN type I signaling.
  • animal; verified against its paper; no independent support found in this corpus; source: Targeting KRAS Inhibitor–Resistant Pancreatic Cancer with an MUC1-C Antibody–Drug Conjugate (2025-10-14, P16)
  • Own paper:
    • claim: "An anti-MUC1-C antibody-drug conjugate is highly effective against MRTX1133-resistant PDAC KRAS G12D models" / paper: "we demonstrate that an anti-M1C ADC is highly effective against MRTX1133-resistant PDAC KRAS G12D cell lines and patient-derived organoid and patient-derived xenograft models." — Targeting KRAS Inhibitor–Resistant Pancreatic Cancer with an MUC1-C Antibody–Drug Conjugate (2025-10-14, P16). Same ADC effect and same MUC1-C IFN type I resistance mechanism. [R4058]
• C03 MUC1-C confers osimertinib and TKI resistance in NSCLC by driving a STAT1/IFN-driven inflammatory memory response, and M1C ADC targets TKI-refractory NSCLC.
  • in vitro; verified against its paper; no independent support found in this corpus; source: MUCIN 1 confers inflammatory memory of tyrosine kinase inhibitor resistance in non-small cell lung cancer (2025-11-27, P11)
  • Own paper:
    • claim: "MUC1-C confers osimertinib and TKI resistance in NSCLC by driving a STAT1/IFN-driven inflammatory memory response" / paper: "We report that the oncogenic MUC1-C/M1C protein confers resistance to osimertinib by regulating the STAT1 and interferon (IFN) type I/II pathways." — MUCIN 1 confers inflammatory memory of tyrosine kinase inhibitor resistance in non-small cell lung cancer (2025-11-27, P11). Paper reports the same MUC1-C STAT1/IFN resistance mechanism and M1C ADC targeting. [R4037]

Aaron Matthew LeBeau, University of Wisconsin–Madison

• C16 Eliminating FAP-expressing cancer-associated fibroblasts with the antibody-drug conjugate huB12-MMAE shifts the tumor microenvironment toward a proinflammatory, antitumor immune state. Reported effect: huB12-MMAE significantly prolonged survival in vivo; no numeric effect sizes stated in the abstract.
  • animal; verified against its paper; no independent support found in this corpus; source: Mechanistic Characterization of Cancer-associated Fibroblast Depletion via an Antibody–Drug Conjugate Targeting Fibroblast Activation Protein (2024-05-15, P40)
  • Own paper:
    • claim: "Eliminating FAP-expressing cancer-associated fibroblasts with the antibody-drug conjugate huB12-MMAE shifts the tumor microenvironment toward a proinflammatory" / paper: "The direct elimination of FAP-expressing CAFs disrupts the cross-talk with cancer cells leading to a proinflammatory response and alterations in the immune microenvironment" — Mechanistic Characterization of Cancer-associated Fibroblast Depletion via an Antibody–Drug Conjugate Targeting Fibroblast Activation Protein (2024-05-15, P40). Paper reports huB12-MMAE elimination of FAP CAFs leading to a proinflammatory response and prolonged survival in vivo. [R4050]
• C18 Anti-FAP VNAR-Fc fusion proteins isolated from an immunized nurse shark library recognize FAP with high affinity, internalize into FAP-positive cells, and serve as theranostic platform constructs. Reported effect: All four VNAR-Fc constructs recognized FAP with high affinity and were rapidly internalized; no numerical values stated in abstract.
  • animal; verified against its paper; no independent support found in this corpus; source: The characterization of variable new antigen receptors targeting FAP isolated from a novel immunized library (2025-08-13, P01)
  • Own paper:
    • claim: "recognize FAP with high affinity, internalize into FAP-positive cells, and serve as theranostic platform constructs" / paper: "We investigated four VNAR-Fc fusion proteins for theranostic properties and found that all four recognized FAP with high affinity and were rapidly internalized by FAP-positive cells." — The characterization of variable new antigen receptors targeting FAP isolated from a novel immunized library (2025-08-13, P01). Same nurse shark VNAR-Fc constructs and findings. [R4052]

John M. Maris, University of Pennsylvania

• C05 The B7-H3-targeting antibody-drug conjugate m276-SL-PBD has significant antitumor activity across a broad panel of pediatric solid tumor PDX models. Reported effect: 92.3% response rate and 61.5% MCR in randomized trials; 91.5% overall response and 64.4% MCR in single mouse trial; 5.5% treatment-related mortality.
  • animal; verified against its paper; no independent support found in this corpus; source: The B7-H3–Targeting Antibody–Drug Conjugate m276-SL-PBD Is Potently Effective Against Pediatric Cancer Preclinical Solid Tumor Models (2021-02-22, P10)
  • Own paper:
    • claim: "has significant antitumor activity across a broad panel of pediatric solid tumor PDX models" / paper: "m276-SL-PBD has significant antitumor activity across a broad panel of pediatric solid tumor PDX models." — The B7-H3–Targeting Antibody–Drug Conjugate m276-SL-PBD Is Potently Effective Against Pediatric Cancer Preclinical Solid Tumor Models (2021-02-22, P10). Same conclusion; the 92.3%, 61.5%, 91.5%, 64.4% and 5.5% figures all match. [R4039]
• C12 ALCAM promotes neuroblastoma cell growth, is transcriptionally driven by MYCN binding at its promoter, and is a potential immunotherapeutic target for the ALCAM-targeted antibody-drug conjugate CX-2009. Reported effect: CX-2009 delayed tumor growth in two of three patient-derived xenograft models; no effect sizes stated in abstract.
  • animal; verified against its paper; no independent support found in this corpus; source: Defining the Functional Role and Potential as an Immunotherapeutic Target of ALCAM in Neuroblastoma (2025-11-07, P34)
  • Own paper:
    • claim: "CX-2009 delayed tumor growth in two of three patient-derived xenograft models" / paper: "CX-2009 (praluzatamab ravtansine), which delayed tumor growth in two of three patient-derived xenograft models." — Defining the Functional Role and Potential as an Immunotherapeutic Target of ALCAM in Neuroblastoma (2025-11-07, P34). Same findings on ALCAM growth role, MYCN promoter binding and CX-2009 xenograft effect. [R4046]

Jiyuan Yang, University of Utah

• C09 U6244-051, an anti-PD-L1 antibody conjugated to HPMA copolymer-epirubicin, prolongs survival and induces durable immunity in advanced murine ovarian cancer. Reported effect: 100 % survival at day 100; drug-to-antibody ratio approximately 30–40.
  • animal; verified against its paper; no independent support found in this corpus; source: PD-L1 targeted antibody-polymer-Epirubicin conjugate prolongs survival in a preclinical murine model of advanced ovarian cancer (2025-04-04, P14)
  • Own paper:
    • claim: "prolongs survival and induces durable immunity in advanced murine ovarian cancer" / paper: "U6244-051 treatment resulted in 100 % survival at day 100, despite initiation at an advanced disease stage." — PD-L1 targeted antibody-polymer-Epirubicin conjugate prolongs survival in a preclinical murine model of advanced ovarian cancer (2025-04-04, P14). Same compound, murine model, 100% survival at day 100 and DAR of 30-40. [R4043]
• C14 CD38-targeted polymer-antibody drug conjugates (ISA-P-EPI and DARA-P-EPI), with HPMA copolymer-epirubicin attached to isatuximab or daratumumab, enhance efficacy against multiple myeloma while preserving antibody function. Reported effect: pADCs effective in 5 out of 8 primary samples; all treated mice remained alive at 100 days in NRG mouse model.
  • animal; verified against its paper; no independent support found in this corpus; source: CD38-targeted antibody-polymer drug conjugates for enhanced treatment of multiple myeloma (2025-06-04, P19)
  • Own paper:
    • claim: "pADCs effective in 5 out of 8 primary samples" / paper: "pADCs were effective in 5 out of 8 primary samples, with their efficacy closely correlating with CD38 surface expression levels." — CD38-targeted antibody-polymer drug conjugates for enhanced treatment of multiple myeloma (2025-06-04, P19). Same ISA-P-EPI and DARA-P-EPI conjugates, 5 of 8 samples and 100-day survival in the NRG mouse model. [R4048]

Patrícia M. R. Pereira, Washington University in St. Louis

• C10 S1PR1 expression is associated with resistance to HER2-targeted therapy in gastric cancer, and combining fingolimod with T-DXd enhances efficacy in HER2+/S1PR1+ tumors. Reported effect: Fingolimod combined with T-DXd "significantly enhanced therapeutic efficacy" in HER2+/S1PR1+ tumors, with reduced tumor volume; no numeric values stated.
  • animal; verified against its paper; no independent support found in this corpus; source: Imaging and targeting S1PR1 in HER2+ tumors (2025-08-07, P32)
  • Own paper:
    • claim: "S1PR1 expression is associated with resistance to HER2-targeted therapy in gastric cancer" / paper: "The S1PR1 inhibitor fingolimod, when combined with T-DXd, significantly enhanced therapeutic efficacy in HER2+/S1PR1+ tumors" — Imaging and targeting S1PR1 in HER2+ tumors (2025-08-07, P32). Paper reports both the S1PR1 resistance association and the fingolimod plus T-DXd enhancement. [R4044]
• C23 Combining lovastatin (to raise surface HER2) with neratinib (to enhance internalization) boosts T-DM1 internalization, lowers HER2 levels and phosphorylation, and sustains efficacy in HER2+ gastric cancer.
  • animal; verified against its paper; no independent support found in this corpus; source: Modulation of HER2 internalization enhances single-dose antibody-drug potency in HER2+ gastric cancer (2025-05-15, P23)
  • Own paper:
    • claim: "boosts T-DM1 internalization, lowers HER2 levels and phosphorylation, and sustains efficacy in HER2+ gastric cancer" / paper: "A decrease in HER2 protein levels and HER2 phosphorylation was detected in cells treated with T-DM1/lovastatin/neratinib when compared to control and T-DM1-only groups." — Modulation of HER2 internalization enhances single-dose antibody-drug potency in HER2+ gastric cancer (2025-05-15, P23). Same lovastatin and neratinib combination with T-DM1 in HER2+ gastric cancer. [R4057]

Natarajan Muthusamy, The Ohio State University

• C21 A humanized anti-ROR1 antibody-drug conjugate, huXBR1-402-G5-PNU, is cytotoxic to proliferating ROR1+ malignant cells and extends survival in mice with human ROR1+ leukemia.
  • animal; verified against its paper; no independent support found in this corpus; source: The ROR1 antibody-drug conjugate huXBR1-402-G5-PNU effectively targets ROR1+ leukemia (2021-08-20, P07)
  • Own paper:
    • claim: "is cytotoxic to proliferating ROR1+ malignant cells and extends survival in mice with human ROR1+ leukemia" / paper: "We found that huXBR1-402-G5-PNU is cytotoxic to proliferating ROR1+ malignant cells in vitro and suppressed leukemia proliferation and extended survival in multiple models of mice engrafted with human ROR1+ leukemia." — The ROR1 antibody-drug conjugate huXBR1-402-G5-PNU effectively targets ROR1+ leukemia (2021-08-20, P07). Paper states the same cytotoxicity and survival extension in mice. [R4055]

Monica Shokeen, Washington University in St. Louis

• C19 Daratumumab conjugated to mertansine (DM1) via a non-cleavable linker and labelled with IRDye800 (DARA-DM1-IR) enhances tumor-killing of native DARA and allows NIR visualization of tumor targeting.
  • animal; verified against its paper; no independent support found in this corpus; source: Tissue biodistribution and tumor targeting of near-infrared labelled anti-CD38 antibody-drug conjugate in preclinical multiple myeloma (2021-09-28, P06)
  • Own paper:
    • claim: "enhances tumor-killing of native DARA and allows NIR visualization of tumor targeting" / paper: "DM1 enhanced tumor-killing efficacy of the native DARA" — Tissue biodistribution and tumor targeting of near-infrared labelled anti-CD38 antibody-drug conjugate in preclinical multiple myeloma (2021-09-28, P06). Same DARA-DM1 conjugate with enhanced killing of native DARA. [R4089]

Andrew Tsourkas, University of Pennsylvania

• C08 A near-traceless proximity-based sortase A conjugation method, fused to an antibody-binding domain, site-specifically labels lysines on native human IgG1 for ADC production. Reported effect: Labeling limited to five lysines on heavy chain and one on light chain of human IgG1; ADCs retain antigen and Fc-receptor binding and show potent cytolytic activity.
  • in vitro; verified against its paper; no independent support found in this corpus; source: Efficient Labeling of Native Human IgG by Proximity-Based Sortase-Mediated Isopeptide Ligation (2021-05-24, P41)
  • Own paper:
    • claim: "Labeling limited to five lysines on heavy chain and one on light chain of human IgG1" / paper: "Antibody labeling is limited to five lysine residues on the heavy chain and one on the light chain of human IgG1." — Efficient Labeling of Native Human IgG by Proximity-Based Sortase-Mediated Isopeptide Ligation (2021-05-24, P41). Same sortase A near-traceless method and same lysine counts. [R4042]
• C13 Photoreactive antibody-binding domain-drug conjugates (oYo-Link) enable rapid site-specific labeling of off-the-shelf antibodies, and ADC potency depends on the antibody, payload, and cell line combination. Reported effect: Cetuximab most potent against A431; clones 425 and 528 most cytotoxic against A549 and MDA-MB-231; drug-to-antibody ratio of ~2 reported.
  • in vitro; verified against its paper; no independent support found in this corpus; source: Exploring the Sensitivity of Antibody–Drug Conjugate Efficacy to the Selection of Payload, Antibody, and Cell line (2024-01-04, P48)
  • Own paper:
    • claim: "ADC potency depends on the antibody, payload, and cell line combination" / paper: "ADC potency toward a given target is dependent on both the antibody and drug chosen" — Exploring the Sensitivity of Antibody–Drug Conjugate Efficacy to the Selection of Payload, Antibody, and Cell line (2024-01-04, P48). Same oYo-Link finding that ADC potency depends on the antibody and drug chosen. [R4088]

Framed read (unvalidated: one model's synthesis of the records above)

Claim that carries the most weight: C07. C07 is the only claim on the sheet that describes a general mechanism (co-administered low-affinity, high-avidity antibody tuning ADC delivery to target expression) rather than one compound's result, and C04 from the same lab describes a related co-administration effect. If the mechanism does not hold outside the originating lab, both claims from that lab lose their shared support.

What would have to hold:

• The mouse efficacy gain reported in R4041 (greater ADC efficacy across a range of HER2 expression levels) must hold in models beyond the immunodeficient ones described; no record covers this.
• The tuning of delivery to local target expression must be shown directly, not only inferred from efficacy; R4041 quotes an efficacy result only, and no record covers the delivery measurement.
• The co-administration effect must reproduce outside the originating lab; every record on the sheet, including R4041 and R4038, has independent set to false, so no independent paper in this pack addresses it.
• The C04 pattern in R4038 (efficacy rising with unconjugated antibody dose until tumor saturation) must be consistent with C07 and not a separate artifact of one construct; no record covers whether the two claims share the same constructs.
• No record covers safety or normal-tissue exposure when unconjugated or low-affinity antibody is co-administered with an ADC.

Questions a data room would have to answer:

• (C07) Provide the raw tumor-volume and survival data per HER2 expression level for the HALA plus ADC arms versus ADC alone, including how expression level was measured and how many animals were in each arm.
• (C07) What direct measurement (imaging, biodistribution, internalization assay) shows that HALA co-administration changed cellular ADC delivery in step with local HER2 expression, as opposed to changing efficacy through another route?
• (C07) Has any group outside the originating lab run HALA co-administration with a HER2 ADC, and if so with which ADC, payload and models?
• (C07) What is the dosing window for the HALA antibody, and what happens to efficacy and to HER2-expressing normal tissue when it is mis-dosed?
• (C04) The reported benefit rises with unconjugated antibody dose until tumor saturation; at what dose was saturation reached, and was a dose that harmed efficacy or tolerability ever observed?
• (C04) No numeric values are stated for the IKS04 co-administration result; provide the tumor-growth curves, group sizes and statistics behind the claim of increased in vivo efficacy.
• (C23) For the lovastatin plus neratinib plus T-DM1 combination, what dose and exposure of each drug was used in the animal work, and are those exposures achievable in patients at tolerated doses?
• (C10) No numeric values are stated for fingolimod plus T-DXd; provide tumor volumes, group sizes and the S1PR1 scoring method used to define the HER2+/S1PR1+ tumors.

Cannot say:

• These records cannot say whether any claim is correct beyond what its own paper states, because every record on the sheet comes from the claim's own paper and none is independent.
• No independent paper in this pack addresses any claim, so the pack gives no view on whether results hold in other labs, models or patient populations.
• The records cannot say anything about manufacturing, intellectual property, cost, competing programs or commercial readiness of any lab or compound.
• Animal and in vitro claims cannot be read as evidence of human efficacy or safety; only the claims marked human tier come from clinical reports.
• The records cannot say whether the quoted abstracts reflect the full data, since several claims state no numeric effect sizes.

What was not shown

• Claims with no checked record: none.
• Records proposed: 26; 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-dfa64eda28; 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