CAR-37 T Cells / Massachusetts General Hospital - LARVOL DELTA

Combining MCL-1 inhibition and CD37-directed chimeric antigen receptor T cells as an effective strategy to target T-cell lymphoma. (PubMed, Leukemia) - "In TCL models with dependence on MCL-1, combining CAR-37 T cells and the MCL-1 inhibitor AZD5991 increases anti-TCL response and prolongs survival of xenografted mice. These findings suggest that personalized selection of BH3 mimetic/CAR-T combinations could maximize the therapeutic index for patients with TCL and possibly other diseases."

IO biomarker • Journal • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CD37

Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies. (PubMed, Blood) - P1 | "Three patients experienced prolonged and severe pancytopenia, and in two of these patients, efforts to ablate CAR-37 T-cells (which were engineered to co-express truncated EGFR) with cetuximab, were unsuccessful. In conclusion, CAR-37 T-cells exhibited anti-tumor activity, with significant CAR expansion and cytokine production. CAR-37 T-cells may be an effective therapy in hematologic malignancies as a bridge to hematopoietic stem cell transplant."

Journal • P1 data • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Transplantation • CD37 • EGFR • IL18

Combinatorial Effects of BH3 Mimetics and CAR T Cells Targeting T-Cell Lymphomas (ASH 2022) - P1 | "First, we did not observe a reduction in CAR-37 T cell viability when cultured in vitro in the presence of TCL target cells and either venetoclax 0.5μM, navitoclax 0.5μM, or AZD5991 0.1μM for 48 hours. These results could be used to nominate and/or deprioritize future combination strategies both for TCL and for other patients being treated with effector T cells for a range of hematologic malignancies. AZD5991 was kindly provided by AstraZeneca."

CAR T-Cell Therapy • IO biomarker • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Prolymphocytic Leukemia • T Cell Non-Hodgkin Lymphoma • Transplantation • BCL2 • BCL2L1 • CSF2 • HAVCR2 • IFNG • LAG3 • PD-1

Phase 1 Study of CD37-Directed CAR T Cells in Patients with Relapsed or Refractory CD37+ Hematologic Malignancies (ASH 2021) - P1 | "Subjects undergo lymphodepletion with fludarabine and cyclophosphamide, then receive CART37 as a single infusion...Two subjects had primary refractory double-hit high-grade B cell lymphoma (HGBCL) that had relapsed after commercial CD19 CAR-T; one subject had cutaneous T cell lymphoma relapsed after extracorporeal photopheresis, alemtuzumab, total skin electron beam radiation, allogeneic hematopoietic stem cell transplant (HSCT), brentuximab, and donor lymphocyte infusion, and one subject had Hodgkin’s lymphoma refractory to six prior regimens, including chemotherapy, brentuximab vedotin, nivolumab and everolimus...Two subjects (who received ≥ 100 x 10 6 CART37 had robust expansion and developed prolonged pancytopenia with marrow aplasia; cetuximab infusion decreased detection of truncated EGFR on circulating T cells but had no impact on vector copy number... In this initial cohort, CART37 infusion resulted in CRS or ICANs as is common for CAR T cell products. Bone..."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Aplastic Anemia • Bone Marrow Transplantation • Cutaneous T-cell Lymphoma • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Transplantation • CD19 • EGFR