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recruiting","href":"/trials/nct04792489/"},{"record":"nct04844866","field":"status","kind":"trial","state":"development","label":"Efficacy and Safety of MB-CART2019.1 vs. SoC in Lymphoma Patients: phase 2, recruiting","href":"/trials/nct04844866/"},{"record":"nct06508931","field":"status","kind":"trial","state":"development","label":"Safety and Efficacy Study of Zamtocabtagene Autoleucel (MB-CART2019.1) in Pediatric Patients With R/R B-Cell Neoplasms: phase 2, recruiting","href":"/trials/nct06508931/"},{"record":"registry:zamtocabtagene-autoleucel","kind":"registry","state":"development","label":"ClinicalTrials.gov: 4 recruiting, active or planned studies (fetched 2026-09-21)","href":"/drugs/zamtocabtagene-autoleucel/#registry"}],"reasons":[]},{"id":"zevorcabtagene-autoleucel","name":"Zevorcabtagene autoleucel","route":"/drugs/zevorcabtagene-autoleucel/","status":"approved","modality":"Cell therapy (autologous BCMA CAR-T, fully human binder)","state":"approved","confidence":"medium","fields":["targets","mechanism","modality"],"components":{"target":{"id":"bcma","name":"BCMA","href":"/targets/bcma/","confidence":"high","from":["targets"],"detail":null},"costim":{"id":"4-1bb","name":"4-1BB","href":"/targets/cd137/","confidence":"high","from":["mechanism","modality"],"detail":null},"cellSource":{"id":"autologous","name":"Autologous","href":"/technologies/car-t-manufacturing-process/","confidence":"high","from":["mechanism","modality"],"detail":null},"cellType":{"id":"t","name":"T cell","href":"/technologies/car-t/","confidence":"medium","from":["modality","mechanism"],"detail":null}},"evidence":[{"record":"zevorcabtagene-autoleucel","field":"status","kind":"drug","state":"approved","label":"Drug record status: approved","href":"/drugs/zevorcabtagene-autoleucel/"},{"record":"zevorcabtagene-autoleucel","field":"approvals[0]","kind":"approval","state":"approved","label":"China 2024: Relapsed or refractory multiple myeloma after three or more lines including a proteasome inhibitor and an immunomodulatory agent","href":"/drugs/zevorcabtagene-autoleucel/"},{"record":"zevorcabtagene-autoleucel","field":"regional.CN","kind":"regional","state":"approved","label":"NMPA (CN): approved 2024","href":"https://english.nmpa.gov.cn/"},{"record":"nct03915184","field":"status","kind":"trial","state":"development","label":"Clinical Trial to Evaluate Zevor-cel (CT053) in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 2): phase 1/2, active","href":"/trials/nct03915184/"},{"record":"registry:zevorcabtagene-autoleucel","kind":"registry","state":"development","label":"ClinicalTrials.gov: 1 recruiting, active or planned study (fetched 2026-09-21)","href":"/drugs/zevorcabtagene-autoleucel/#registry"}],"reasons":[]}],"unresolved":[{"id":"ard103","name":"ARD103","route":"/drugs/ard103/","format":"car-t","modality":"CAR-T cell therapy","missing":["target","costim","binder","cellSource","vector"],"why":"No target on the record: the targets field is empty and the modality and mechanism text name none the corpus knows."}],"stopped":[],"proposed":[{"id":"car-cldn18-2-cd28","format":"car-t","name":"Claudin 18.2 CAR-T with CD28 costimulation","a":"cldn18-2","b":"cd28","raw":{"a":"cldn18-2","b":"cd28"},"matched":true,"unmatched":[],"rationale":"Claudin 18.2 is validated by the first approved solid-tumour CAR-T (satricabtagene-autoleucel), which uses 4-1BB costimulation, and CD28 is validated as a costimulatory domain in approved CD19 CAR-Ts (axicabtagene-ciloleucel). No corpus Claudin 18.2 CAR-T uses CD28, so the cell is untried. Solid-tumour CAR-Ts need to expand quickly against an immunosuppressive microenvironment, which favours CD28's kinetics; the risk is stronger on-target gastric mucosal toxicity from the same rapid activation.","caveat":"The 4-1BB construct already causes gastric mucosal injury; a CD28 version would need to show that faster expansion buys response without worse mucosal toxicity.","status":"no public evidence","statusLabel":"No public evidence","score":{"total":73,"burden":31,"worldDeaths":1127584,"validationA":15,"validationB":15,"plausibility":12},"evidence":[{"label":"Trial: Legend Biotech USA Inc (2022-09-14), neighbouring cell","url":"https://clinicaltrials.gov/study/NCT05539430","quote":"This is a Phase 1, Open-Label, Dose Escalation and Expansion, Multicenter Study of Claudin 18.2-Targeted Chimeric Antigen Receptor T-cells in Subjects with Unresectable, Locally Advanced, or Metastatic Gastric, Gastroesophageal Junction (GEJ), Esophageal, or Pancreatic Adenocarcinoma","kind":"trial","adjacent":true},{"label":"Paper: Lee HJ et al. (2024-05-03), neighbouring cell","url":"https://doi.org/10.1007/s12275-024-00133-0","quote":"Genetically Engineered CLDN18.2 CAR-T Cells Expressing Synthetic PD1/CD28 Fusion Receptors Produced Using a Lentiviral Vector.","kind":"paper","adjacent":true}],"refs":["axicabtagene-ciloleucel","satricabtagene-autoleucel"],"cancers":["gastric-cldn18-2-positive","gastric","pancreatic"],"proposedBy":"OnCo open pipeline","on":"2026-09-23"},{"id":"car-met-4-1bb","format":"car-t","name":"MET CAR-T with 4-1BB costimulation","a":"met","b":"4-1bb","raw":{"a":"met","b":"4-1bb"},"matched":true,"unmatched":[],"rationale":"MET is validated by an approved ADC (telisotuzumab-vedotin) and kinase inhibitors (capmatinib), and 4-1BB by most approved CAR-Ts (tisagenlecleucel). No corpus CAR-T targets MET. MET is expressed on hepatocytes and many epithelia, so a systemic MET CAR-T risks liver toxicity; intratumoural or transient mRNA CAR delivery is the design that has been tried.","caveat":"Hepatocyte MET expression is the obstacle; unless a transient or locally delivered product proves safe, this stays preclinical.","status":"clinical evidence","statusLabel":"Clinical evidence","score":{"total":73,"burden":35,"worldDeaths":3242297,"validationA":15,"validationB":15,"plausibility":8},"evidence":[{"label":"Trial: University of Pennsylvania (2013-04-23)","url":"https://clinicaltrials.gov/study/NCT01837602","quote":"An open-label, clinical trial of autologous cMet redirected T cells administered intratumorally (IT) in patients with breast cancer.","kind":"trial"},{"label":"Trial: University of Pennsylvania (2017-02-23)","url":"https://clinicaltrials.gov/study/NCT03060356","quote":"This is a pilot study to evaluate feasibility, safety, and preliminary evidence of efficacy for intravenously administered, RNA electroporated autologous T cells expressing MET chimeric antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) co-stimulatory domains (referred to as \"RNA CART-cMET\") in patients with advanced melanoma or breast carcinoma.","kind":"trial"},{"label":"Paper: Su C et al. (2025-08-11)","url":"https://doi.org/10.1038/s41598-025-15086-6","quote":"Co-expression of a truncated TGFβ receptor II in c-Met CAR T cells enhances antitumor activity against lung adenocarcinoma.","kind":"paper"}],"refs":["capmatinib","telisotuzumab-vedotin","tisagenlecleucel"],"cancers":["tnbc","hcc","met-altered-nsclc"],"proposedBy":"OnCo open pipeline","on":"2026-09-23"},{"id":"car-trop2-4-1bb","format":"car-t","name":"TROP2 CAR-T with 4-1BB costimulation","a":"trop2","b":"4-1bb","raw":{"a":"trop2","b":"4-1bb"},"matched":true,"unmatched":[],"rationale":"TROP2 carries three approved ADCs (sacituzumab-govitecan, datopotamab-deruxtecan, sacituzumab-tirumotecan) and 4-1BB is the costimulatory domain of most approved CAR-Ts (tisagenlecleucel). The corpus holds a TROP2 CAR-NK in phase 2 (eb-nk-301) but no TROP2 CAR-T. TROP2 is broadly expressed on normal epithelia, so a CAR-T's sustained killing would hit skin and gut; the ADCs tolerate this because payload dose scales with antigen density, but a CAR has no such threshold unless engineered with logic gating.","caveat":"Normal-epithelium expression makes an unmodified TROP2 CAR-T dangerous; logic-gated or transient constructs are the only credible designs.","status":"preclinical evidence","statusLabel":"Preclinical","score":{"total":73,"burden":35,"worldDeaths":3171577,"validationA":15,"validationB":15,"plausibility":8},"evidence":[{"label":"Paper: Brea EJ et al. (2025-11-01)","url":"https://doi.org/10.1158/2326-6066.cir-25-0527","quote":"Systematic Engineering of TROP2-Targeted CAR T-Cell Therapy Overcomes Resistance Pathways in Solid Tumors.","kind":"paper"},{"label":"Paper: Sun S et al. (2025-09-03)","url":"https://doi.org/10.1136/jitc-2025-012442","quote":"Preclinical evaluation of antitumor activity and toxicity of TROP2-specific CAR-T cells for treatment of triple-negative breast cancer.","kind":"paper"},{"label":"Trial: M.D. Anderson Cancer Center (2026-04-28), neighbouring cell","url":"https://clinicaltrials.gov/study/NCT07553390","quote":"TGFBR2 KO iC9/TROP2.CAR/IL-15 NK cells.","kind":"trial","adjacent":true}],"refs":["datopotamab-deruxtecan","eb-nk-301","sacituzumab-govitecan","sacituzumab-tirumotecan","tisagenlecleucel"],"cancers":["tnbc","pancreatic","nsclc","urothelial"],"proposedBy":"OnCo open pipeline","on":"2026-09-23"},{"id":"car-her2-4-1bb","format":"car-t","name":"HER2 CAR-T with 4-1BB costimulation","a":"her2","b":"4-1bb","raw":{"a":"her2","b":"4-1bb"},"matched":true,"unmatched":[],"rationale":"HER2 is the corpus's most validated delivery antigen (trastuzumab-deruxtecan, trastuzumab, zanidatamab) and 4-1BB costimulation is validated in most approved CAR-Ts (tisagenlecleucel, ciltacabtagene-autoleucel). No corpus CAR-T targets HER2. HER2 is expressed at low levels on lung and heart, and a high-affinity HER2 CAR caused a fatal respiratory event in 2010; later low-affinity constructs have been tolerated, so the design question is affinity tuning and local (intraventricular, intratumoural) delivery.","caveat":"On-target lung and heart toxicity is documented for a high-affinity HER2 CAR; any new construct needs affinity tuning or regional delivery, and paediatric sarcoma or CNS disease is a more plausible first indication than breast cancer.","status":"clinical evidence","statusLabel":"Clinical evidence","score":{"total":72,"burden":32,"worldDeaths":1574778,"validationA":15,"validationB":15,"plausibility":10},"evidence":[{"label":"Trial: City of Hope Medical Center (2018-10-04)","url":"https://clinicaltrials.gov/study/NCT03696030","quote":"This phase I trial studies the side effects and best dose of HER2-CAR T cells in treating patients with cancer that has spread to the brain or leptomeninges and has come back (recurrent).","kind":"trial"},{"label":"Trial: Fate Therapeutics (2024-02-05)","url":"https://clinicaltrials.gov/study/NCT06241456","quote":"This is a phase 1 study designed to evaluate the safety, tolerability, and antitumor activity of FT825 (also known as ONO-8250) with or without monoclonal antibody therapy following chemotherapy in participants with advanced human epidermal growth factor receptor 2 (HER2)-positive or other advanced solid tumors.","kind":"trial"},{"label":"Paper: Murayama Y et al. (2021-09-21)","url":"https://doi.org/10.1016/j.tranon.2021.101227","quote":"Effectiveness of 4-1BB-costimulated HER2-targeted chimeric antigen receptor T cell therapy for synovial sarcoma.","kind":"paper"}],"refs":["ciltacabtagene-autoleucel","tisagenlecleucel","trastuzumab","trastuzumab-deruxtecan","zanidatamab"],"cancers":["breast-her2-positive","gastric-her2-positive","osteosarcoma","glioblastoma"],"proposedBy":"OnCo open pipeline","on":"2026-09-23"},{"id":"car-sstr2-4-1bb","format":"car-t","name":"Somatostatin receptor 2 CAR-T with 4-1BB costimulation","a":"sstr2","b":"4-1bb","raw":{"a":"sstr2","b":"4-1bb"},"matched":true,"unmatched":[],"rationale":"SSTR2 is validated by an approved radioligand (lutathera) and 4-1BB by most approved CAR-Ts (tisagenlecleucel). No corpus CAR-T targets SSTR2. SSTR2 is a seven-transmembrane GPCR with a small extracellular surface, which is hard for an scFv to bind; a CAR built on the octreotide peptide as the binder is the plausible design, and SSTR2 on pancreatic islets and pituitary is the safety question.","caveat":"Islet and pituitary expression could give endocrine toxicity, and a GPCR is a difficult CAR target; preclinical work on a peptide-based binder would need to come first.","status":"preclinical evidence","statusLabel":"Preclinical","score":{"total":71,"burden":33,"worldDeaths":1817469,"validationA":15,"validationB":15,"plausibility":8},"evidence":[{"label":"Paper: Pellegrino C et al. (2024-10-03)","url":"https://doi.org/10.1080/2162402x.2024.2412371","quote":"Peptide-guided adaptor-CAR T-Cell therapy for the treatment of SSTR2-expressing neuroendocrine tumors.","kind":"paper"},{"label":"Paper: Chen J et al. (2026-01-01)","url":"https://doi.org/10.1093/noajnl/vdag186","quote":"A fluorescein-conjugated somatostatin receptor antagonist adapter for chimeric antigen receptor T cell therapy of meningioma.","kind":"paper"}],"refs":["lutathera","tisagenlecleucel"],"cancers":["neuroendocrine","sclc","pancreatic-net"],"proposedBy":"OnCo open pipeline","on":"2026-09-23"},{"id":"car-nectin4-4-1bb","format":"car-t","name":"Nectin-4 CAR-T with 4-1BB costimulation","a":"nectin4","b":"4-1bb","raw":{"a":"nectin4","b":"4-1bb"},"matched":true,"unmatched":[],"rationale":"Nectin-4 is validated by an approved ADC (enfortumab-vedotin) and 4-1BB by most approved CAR-Ts (tisagenlecleucel). No corpus CAR-T targets Nectin-4. Nectin-4 is dense and fairly homogeneous in urothelial cancer, and its normal expression is mainly skin; the skin toxicity of enfortumab-vedotin shows the antigen is reachable there, so a CAR-T would need affinity tuning to spare keratinocytes.","caveat":"Keratinocyte expression predicts skin toxicity worse than enfortumab's; whether affinity tuning can separate tumour from skin is the first preclinical question.","status":"clinical evidence","statusLabel":"Clinical evidence","score":{"total":69,"burden":29,"worldDeaths":886699,"validationA":15,"validationB":15,"plausibility":10},"evidence":[{"label":"Trial: Shenzhen Celconta Life Science Co., Ltd. (2024-12-09)","url":"https://clinicaltrials.gov/study/NCT06724835","quote":"Treating Nectin-4-positive Advanced Breast Cancer with XKDCT293 (Nectin-4-CAR-T)","kind":"trial"},{"label":"Trial: changjianhua (2025-08-03)","url":"https://clinicaltrials.gov/study/NCT07101549","quote":"Treating Nectin-4-positive Advanced Solid Tumors With R-Star001 (Nectin-4-CART-IL18)","kind":"trial"},{"label":"Paper: Ma L et al. (2025-12-04)","url":"https://doi.org/10.1016/j.ymthe.2025.12.002","quote":"On-target/off-tumor toxicities following infusion of low-affinity Nectin-4-specific CAR T cells.","kind":"paper"},{"label":"Paper: Chang K et al. (2025-09-10)","url":"https://doi.org/10.1038/s41467-025-62710-0","quote":"Modulating the PPARγ pathway upregulates NECTIN4 and enhances chimeric antigen receptor (CAR) T cell therapy in bladder cancer.","kind":"paper"}],"refs":["enfortumab-vedotin","tisagenlecleucel"],"cancers":["urothelial","tnbc"],"proposedBy":"OnCo open pipeline","on":"2026-09-23"},{"id":"car-psma-4-1bb","format":"car-t","name":"PSMA CAR-T with 4-1BB costimulation","a":"psma","b":"4-1bb","raw":{"a":"psma","b":"4-1bb"},"matched":true,"unmatched":[],"rationale":"PSMA is validated by an approved radioligand (pluvicto) and three phase-3 alpha emitters, and 4-1BB is the costimulatory domain of most approved CAR-Ts (tisagenlecleucel, lisocabtagene-maraleucel). No corpus CAR-T targets PSMA, although the corpus already flags armoured CAR designs for solid tumours (armored-car). PSMA is tumour-restricted enough for a radioligand, but prostate cancer's bone-marrow niche and TGF-beta-rich stroma suppress T cells; armoured constructs with dominant-negative TGF-beta receptors are the design that has reached patients.","caveat":"An armoured PSMA CAR-T caused fatal toxicity in an early trial; the balance between enough potency to clear bone metastases and safety is unresolved.","status":"clinical evidence","statusLabel":"Clinical evidence","score":{"total":66,"burden":26,"worldDeaths":397430,"validationA":15,"validationB":15,"plausibility":10},"evidence":[{"label":"Trial: University of Pennsylvania (2017-03-24)","url":"https://clinicaltrials.gov/study/NCT03089203","quote":"This is a single center, single arm Phase I study to establish the safety and feasibility of intravenously administered lentivirally transduced dual PSMA-specific/TGFβ-resistant CAR modified autologous T cells (CART-PSMA-TGFβRDN cells) in patients with metastatic castrate resistant prostate cancer.","kind":"trial"},{"label":"Trial: Tceleron Therapeutics, Inc. (2022-08-05)","url":"https://clinicaltrials.gov/study/NCT05489991","quote":"An open-label, multi-center, Phase 1/2 study to determine the safety, tolerability, and feasibility of dosing adult patients with mCRPC with genetically modified autologous T-cells (TmPSMA-02) engineered to express a CAR capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA) and activating the T-cell.","kind":"trial"},{"label":"Paper: Slovin SF et al. (2026-08-01)","url":"https://doi.org/10.1158/1078-0432.ccr-25-3052","quote":"Phase I Trial of P-PSMA-101 CAR T Cells in Patients with Metastatic Castration-Resistant Prostate Cancer.","kind":"paper"}],"refs":["armored-car","lisocabtagene-maraleucel","pluvicto","tisagenlecleucel"],"cancers":["prostate-mcrpc"],"proposedBy":"OnCo open pipeline","on":"2026-09-23"},{"id":"car-cd123-4-1bb","format":"car-t","name":"CD123 CAR-T with 4-1BB costimulation","a":"cd123","b":"4-1bb","raw":{"a":"cd123","b":"4-1bb"},"matched":true,"unmatched":[],"rationale":"CD123 is validated by an approved ADC (pivekimab-sunirine) and an approved toxin fusion (tagraxofusp), and 4-1BB by most approved CAR-Ts (tisagenlecleucel). No corpus CAR-T targets CD123. CD123 marks leukaemic stem cells and BPDCN uniformly, so the antigen is homogeneous; it is also on endothelium and normal progenitors, and capillary leak from CD123-directed agents (tagraxofusp) is the class toxicity to expect.","caveat":"Capillary leak and myeloablation are the expected toxicities; like CD33, this works best as a bridge to transplant or with a suicide switch.","status":"clinical evidence","statusLabel":"Clinical evidence","score":{"total":65,"burden":25,"worldDeaths":305405,"validationA":15,"validationB":15,"plausibility":10},"evidence":[{"label":"Trial: University of Pennsylvania (2015-12-07)","url":"https://clinicaltrials.gov/study/NCT02623582","quote":"Autologous Anti-CD 123 CAR TCR/4-1BB-expressing T-lymphocytes.","kind":"trial"},{"label":"Trial: St. Jude Children's Research Hospital (2020-03-24)","url":"https://clinicaltrials.gov/study/NCT04318678","quote":"The CD123-CAR T-cell therapy is a new treatment that is being investigated for treatment of AML/myelodysplastic syndrome (MDS), T- or B- acute lymphoblastic leukemia (ALL) or blastic plasmacytoid dendritic cell neoplasia (BPDCN).","kind":"trial"},{"label":"Trial: Cellectis S.A. (2017-06-29)","url":"https://clinicaltrials.gov/study/NCT03203369","quote":"A Phase 1 dose-finding study of Universal Chimeric Antigen Receptor T-cells targeting cluster of differentiation (CD) 123 (UCART123) administered intravenously to patients with relapsed or refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN), followed by a dose expansion phase in relapsed or refractory BPDCN patients or newly diagnosed BPDCN patients.","kind":"trial"}],"refs":["pivekimab-sunirine","tagraxofusp","tisagenlecleucel"],"cancers":["aml","bpdcn"],"proposedBy":"OnCo open pipeline","on":"2026-09-23"},{"id":"car-cd33-4-1bb","format":"car-t","name":"CD33 CAR-T with 4-1BB costimulation","a":"cd33","b":"4-1bb","raw":{"a":"cd33","b":"4-1bb"},"matched":true,"unmatched":[],"rationale":"CD33 is validated by an approved ADC (gemtuzumab-ozogamicin) and 4-1BB by most approved CAR-Ts (tisagenlecleucel). No corpus CAR-T targets CD33, and the transplant-bridge design that would make it safe is already established for CD45 radioimmunotherapy (iomab-b). CD33 is on normal myeloid progenitors, so a persistent CD33 CAR-T causes marrow aplasia; the workable designs are a transient CAR (mRNA), a suicide switch, or CAR-T as a bridge to transplant with CD33-deleted donor stem cells.","caveat":"Marrow aplasia is certain with a persistent CD33 CAR; the therapy only makes sense paired with a transplant plan or an off-switch.","status":"clinical evidence","statusLabel":"Clinical evidence","score":{"total":65,"burden":25,"worldDeaths":305405,"validationA":15,"validationB":15,"plausibility":10},"evidence":[{"label":"Trial: City of Hope Medical Center (2023-01-05)","url":"https://clinicaltrials.gov/study/NCT05672147","quote":"This phase I trial tests the safety, side effects, and the best dose of anti-CD33 chimeric antigen receptor (CAR) T-Cell therapy in treating patients with acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory).","kind":"trial"},{"label":"Trial: Center for International Blood and Marrow Transplant Research (2019-06-03)","url":"https://clinicaltrials.gov/study/NCT03971799","quote":"This phase 1/2 trial aims to determine the safety and feasibility of antiCD33 chimeric antigen receptor (CAR) expressing T cells (CD33CART) in children and adolescents/young adults (AYAs) with relapsed/refractory acute myeloid leukemia (AML).","kind":"trial"},{"label":"Paper: Mushtaq MU et al. (2026-04-01)","url":"https://doi.org/10.1182/blood.2025031053","quote":"A phase 1/2 study of donor-derived anti-CD33 CAR T-cell therapy (VCAR33) for relapsed/refractory AML after allogeneic HCT.","kind":"paper"},{"label":"Paper: Petty NE et al. (2025-05-01), neighbouring cell","url":"https://doi.org/10.1182/bloodadvances.2024015016","quote":"Protection of CD33-modified hematopoietic stem cell progeny from CD33-directed CAR T cells in rhesus macaques.","kind":"paper","adjacent":true}],"refs":["gemtuzumab-ozogamicin","iomab-b","tisagenlecleucel"],"cancers":["aml","all-paediatric-relapsed"],"proposedBy":"OnCo open pipeline","on":"2026-09-23"},{"id":"car-bcma-cd28","format":"car-t","name":"BCMA CAR-T with CD28 costimulation","a":"bcma","b":"cd28","raw":{"a":"bcma","b":"cd28"},"matched":true,"unmatched":[],"rationale":"BCMA is validated by two approved 4-1BB CAR-Ts (idecabtagene-vicleucel, ciltacabtagene-autoleucel) and the CD28 costimulatory domain by two approved CD19 CAR-Ts (axicabtagene-ciloleucel, brexucabtagene-autoleucel). No corpus BCMA CAR-T uses CD28 costimulation, so the cell is untried in the corpus. Every approved BCMA CAR-T uses 4-1BB (idecabtagene-vicleucel, ciltacabtagene-autoleucel); CD28 gives faster, stronger expansion (axicabtagene-ciloleucel) but shorter persistence and more cytokine release, and myeloma relapses are often late, where persistence matters.","caveat":"An earlier CD28 BCMA CAR-T was stopped after phase 1; whether that reflected the domain, the binder or the era's manufacturing is the question to settle before repeating it.","status":"clinical evidence","statusLabel":"Clinical evidence","score":{"total":63,"burden":21,"worldDeaths":121388,"validationA":15,"validationB":15,"plausibility":12},"evidence":[{"label":"Trial: Kite, A Gilead Company (2017-10-24)","url":"https://clinicaltrials.gov/study/NCT03318861","quote":"The primary objective of the study is to evaluate the safety and tolerability of KITE-585, an autologous engineered chimeric antigen receptor (CAR) T-cell product targeting a protein commonly found on myeloma cells called B-cell maturation antigen (BCMA), as measured by the incidence of dose-limiting toxicities (DLTs).","kind":"trial"},{"label":"Paper: Cornell RF et al. (2021-06-15)","url":"https://europepmc.org/article/MED/34249462","quote":"A phase 1, multicenter study evaluating the safety and efficacy of KITE-585, an autologous anti-BCMA CAR T-cell therapy, in patients with relapsed/refractory multiple myeloma.","kind":"paper"}],"refs":["axicabtagene-ciloleucel","brexucabtagene-autoleucel","ciltacabtagene-autoleucel","idecabtagene-vicleucel"],"cancers":["multiple-myeloma","myeloma-relapsed-refractory"],"proposedBy":"OnCo open pipeline","on":"2026-09-23"},{"id":"car-cd38-4-1bb","format":"car-t","name":"CD38 CAR-T with 4-1BB costimulation","a":"cd38","b":"4-1bb","raw":{"a":"cd38","b":"4-1bb"},"matched":true,"unmatched":[],"rationale":"CD38 is validated by two approved antibodies (daratumumab, isatuximab) and 4-1BB by most approved CAR-Ts (tisagenlecleucel). No corpus CAR-T targets CD38, which would offer an autologous option after BCMA and GPRC5D antigen loss. CD38 is on activated T cells themselves, so a CD38 CAR-T risks fratricide during manufacturing unless CD38 is knocked out; affinity-tuned CARs that spare CD38-low normal cells have been described.","caveat":"Fratricide and CD38 expression on NK cells and red-cell precursors are the obstacles; a CD38-knockout T-cell product is the likely requirement.","status":"clinical evidence","statusLabel":"Clinical evidence","score":{"total":61,"burden":21,"worldDeaths":121388,"validationA":15,"validationB":15,"plausibility":10},"evidence":[{"label":"Trial: Chinese PLA General Hospital (2018-12-07)","url":"https://clinicaltrials.gov/study/NCT03767751","quote":"CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory Multiple Myeloma,however, a subset of patients relapse due to the loss of target in tumor cells.Dual Specificity CD38 and BCMA CAR-T cells can recognize and kill the malignant cells through recognition of CD38 or BCMA.","kind":"trial"},{"label":"Paper: Xu X et al. (2026-04-29)","url":"https://doi.org/10.3389/fonc.2026.1744250","quote":"Efficacy and safety of CD38-directed CAR-T cell therapy for multiple myeloma: a systematic review and meta-analysis.","kind":"paper"},{"label":"Paper: Preece R et al. (2025-12-24)","url":"https://doi.org/10.3324/haematol.2025.289016","quote":"Allo-defensive, multiplex base-edited, anti-CD38 CAR T cells for 'off-the-shelf' immunotherapy.","kind":"paper"}],"refs":["daratumumab","isatuximab","tisagenlecleucel"],"cancers":["multiple-myeloma","peripheral-t-cell-lymphoma"],"proposedBy":"OnCo open pipeline","on":"2026-09-23"},{"id":"car-cd30-4-1bb","format":"car-t","name":"CD30 CAR-T with 4-1BB costimulation","a":"cd30","b":"4-1bb","raw":{"a":"cd30","b":"4-1bb"},"matched":true,"unmatched":[],"rationale":"CD30 is validated by an approved ADC (brentuximab-vedotin) and 4-1BB by most approved CAR-Ts (tisagenlecleucel). The corpus holds a CD30 CAR-NK in phase 2 (eb-car30-nk) but no CD30 CAR-T. CD30 is restricted to activated lymphocytes and Reed-Sternberg cells, so normal-tissue toxicity is low; the obstacle is the Hodgkin microenvironment, which excludes T cells, and the small number of patients who fail brentuximab and checkpoint blockade.","caveat":"The population that needs it is small and the Hodgkin microenvironment resists T-cell infiltration; a CCR4-armoured design may be required for cells to reach the tumour.","status":"clinical evidence","statusLabel":"Clinical evidence","score":{"total":60,"burden":14,"worldDeaths":22733,"validationA":15,"validationB":15,"plausibility":16},"evidence":[{"label":"Trial: Tessa Therapeutics (2020-02-13)","url":"https://clinicaltrials.gov/study/NCT04268706","quote":"This is a two-part, Phase 2, multicenter, open-label, single arm study to evaluate the safety and efficacy of autologous CD30.CAR-T in adult and pediatric subjects with relapsed or refractory CD30+ classical Hodgkin Lymphoma.","kind":"trial"},{"label":"Trial: UNC Lineberger Comprehensive Cancer Center (2023-10-19)","url":"https://clinicaltrials.gov/study/NCT06090864","quote":"ATLCAR.CD30.CCR4 for CD30+ HL ATLCAR.CD30.CCR4 Cells","kind":"trial"},{"label":"Paper: Wang X et al. (2026-07-22)","url":"https://doi.org/10.1158/1078-0432.ccr-26-1292","quote":"Long-term follow-up of third generation anti-CD30 CAR T-cell therapy in relapsed/refractory CD30+ lymphomas: a single-arm, multicentre, phase 1-2 trial.","kind":"paper"}],"refs":["brentuximab-vedotin","eb-car30-nk","tisagenlecleucel"],"cancers":["relapsed-refractory-hodgkin-lymphoma","hodgkin-lymphoma","peripheral-t-cell-lymphoma"],"proposedBy":"OnCo open pipeline","on":"2026-09-23"}],"note":"Every state is derived from the records named in evidence; untried means no medicine in this corpus combines the two parts. Proposed cells are hypotheses from the open pipeline (docs/OPEN-PIPELINE.md), not records of a medicine. CC BY-NC 4.0, attribute Data from OnCo (onco.cc). Not medical advice."}