multi-specific CAR-T / Oricell - LARVOL DELTA

Tri-specific autologous CD19.20.22 chimeric antigen receptor (CAR) T-cells for patients with Relapsed/Refractory B-cell lymphomas. (ASH 2025) - "CAR T cell resistance mechanisms include the loss of CD19 expression thus multi-specific CAR-T are a promising strategy to help overcome tumor escape (Schneider, Xiong et al...Patients received cyclophosphamide500mg/m2 and fludarabine 30mg/m2 on days -5 to -3...Prior therapies included BR, RCHOP, commercial CD19 CAR-T therapy, polatuzumab and allo-SCT. Patient 1 was CAR-T-naive, patients 2 and 3 had previously received axi-cel... Four patients were enrolled to receive 1x106 CAR-T/kg. One patient had a manufacturing failure,and three patients were successfully treated. Of these three products, median fold increase in T-cells andviability after expansion was 16.1 (range 13.8-28.1) and 90.6% (range 87.9-94.0), respectively."

Clinical • IO biomarker • Trispecific • B Cell Lymphoma • CNS Disorders • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia • CD19 • CD22 • CD4 • CD8 • ICOS

Optimal trispecific CAR construct simultaneously targets BCMA, GPRC5D, and CD38 to treat antigen-heterogeneous multiple myeloma (ASH 2025) - "Multi-specific CAR-T cells were well tolerated and represent a promising and novel approachfor targeting antigen-heterogeneous MM. Compared to single or bi-specific CARs, these cellsdemonstrated robust anti-tumor activity in vitro and in vivo. Furthermore, incorporation of the JAK/STAT5signaling pathway enhances T-cell fitness and reduces exhaustion."

Heterogeneity • IO biomarker • Trispecific • Hematological Malignancies • Multiple Myeloma • CD38 • STAT5

Armored Multivalent CAR-T Cells Targeting BCMA, GPRC5D, and CD38 Eradicate Antigen-Heterogeneous Multiple Myeloma, Address Antigen Escape and Enhance Expansion (ASH 2024) - "Our findings advocate for further exploration of multi-specific targeting as a promising strategy to facilitate rapid and profound tumor clearance and achieve durable responses in R/R MM, potentially circumventing clonal selection. Further investigation into baseline and longitudinal correlations between immune and tumor profiles with clinical response to the multi-specific CAR-T may provide insights into mechanisms of response and resistance, and inform a development of novel therapy."

CAR T-Cell Therapy • Heterogeneity • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • CD38 • GPRC5D • IL6

Multimodal Atlas of Paired Diagnosis and Relapse AML Reveals Surface Antigens for Multi-Specific Immunotherapy (ASH 2024) - "To demonstrate this on established AML Ags, we developed novel multi-specific CAR-T cells with an "OR" logic gate directed against CD33 and CLL-1...In summary, we integrated rich multimodal data from our atlas with machine learning and performed experimental validation to identify promising single and combinations of AML Ag targets including CD33, CLL-1, LAIR1, ITGA4, LY75, and CD244. These novel combinations can be leveraged to develop new multi-specific agents (e.g. CAR-T cells or ADCs) that better address AML heterogeneity."

IO biomarker • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Oncology • CD123 • CD33 • IL3RA • ITGA4 • LAIR1 • LY75