autologous Car-T cells / Tongji Hospital, Huazhong University of Science and Technology - LARVOL DELTA

A Phase 2 Clinical Trial of Anti-CD19 CAR-T (pCAR-19B) in Chinese Pediatric and Young Adult with Relapsed/Refractory (R/R) CD19+ B-ALL: The First Pivotal Study in an Asian Population (ASH 2024) - P2 | "The chimeric antigen receptor (CAR-T) cell therapy has revolutionized the treatment of relapsed/refractory (R/R) B-cell ALL, with the first FDA-approved product, Kymriah (tisagenlecleucel) developed by Novartis, significantly improving remission rates and survival times. pCAR-19B is an autologous CAR-T cell product with an optimized humanized CD19-specific single-chain variable fragment (scFv) designed to address safety concerns...Conclusions : Despite a heavy burden of BM blasts and a high risk of genetic variations, pCAR-19B demonstrated high remission rates, achieved a high rate of MRD-negative remission, durable responses, and a tolerable safety profile. This study represents the first pivotal clinical trial of childhood B-ALL in an Asian population, offering a new treatment option for Chinese pediatric and young adult patients with R/R B-ALL."

Clinical • P2 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Childhood B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Solid Tumor

Subgroup Analyses of Phase 2 Study: Evaluating the Efficacy of Fully Human BCMA-Targeting CAR T Cells (Zevorcabtagene Autoleucel) in Patients with Relapsed/Refractory Multiple Myeloma (ASH 2024) - P1/2 | "Zevorcabtagene autoleucel (zevor‑cel) is a fully human, BCMA-targeting autologous CAR T-cell therapy...There was a trend towards favorable outcomes which was seen in patients without high-risk cytogenetics compared to those with high-risk cytogenetics : 18m DOR rate of 66% versus 58%, 18m PFS rate of 69% versus 56% and an estimated 30m OS rate of 85% versus 76%, however, none of these differences were statistically significant. Conclusion The subgroup analyses of the pivotal Phase II stage of LUMMICAR STUDY 1 indicated that the clinical efficacy of zevor‑cel is not significantly impacted by baseline characteristics suggesting that even patients with RRMM with poor prognostic factors may benefit from zevor-cel."

CAR T-Cell Therapy • Clinical • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Off-the-shelf CAR-T cell therapies for relapsed or refractory B-cell malignancies: latest update from ASH 2023 annual meeting. (PubMed, J Hematol Oncol) - "Compared with autologous CAR-T cell therapy, off-the-shelf universal CAR-T cell therapies have many potential benefits, such as immediate accessibility for patients, stable quality due to industrialized manufacturing and additional infusions of CAR-T cells with different targets...The most common technological approaches involve modifying healthy donor T cells via gene editing technology and altering different types of T cells. This article summarizes some of the latest data from preclinical and clinical studies of off-the-shelf CAR-T cell therapies in the treatment of R/R B-cell malignancies from the 2023 ASH Annual Meeting (ASH 2023)."

CAR T-Cell Therapy • Journal • Review • Graft versus Host Disease • Hematological Malignancies • Immunology • Oncology

Allogeneic and Autologous Anti-CD7 CAR-T Cell Therapies in Relapsed or Refractory T Cell Malignancies (ASH 2022) - P1 | "Patients underwent lymphodepletion with fludarabine and cyclophosphamide followed by CAR-T infusion at a dose of 1x106 or 2x106/kg on D0...Due to the higher relapse rate in patients receiving autologous CAR-T cells, we recommend consolidation therapy should be considered. For patients with allogeneic CAR-T cells, long-term monitoring and timely intervention for hemogram and infection may significantly improve patients' outcomes. Larger sample size and longer follow-up are needed to confirm this conclusion."

CAR T-Cell Therapy • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Cerebral Hemorrhage • Chronic Graft versus Host Disease • Cutaneous T-cell Lymphoma • Dermatology • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Inflammation • Leukemia • Lymphoma • Mycosis Fungoides • Oncology • Pneumonia • Respiratory Diseases • T Acute Lymphoblastic Leukemia • Thrombocytopenia • Transplantation

Generating universal chimeric antigen receptor expressing cell products from induced pluripotent stem cells: beyond the autologous CAR-T cells. (PubMed, Chin Med J (Engl)) - "Manufacturing hypoimmunogenic iPSCs by inactivation or over-expression at the genetic level and then arming the derived cells with CAR have emerged as a form of "off-the-shelf" strategy to eliminate tumor cells efficiently and safely in a broader range of patients. This review describes the reasonability, feasibility, superiority, and drawbacks of such approaches, summarizes the current practices and relevant research progress, and provides insights into the possible new paths for personalized cell-based therapies."

CAR T-Cell Therapy • IO biomarker • Journal • Hematological Malignancies • Lymphoma • Oncology

Allogeneic CAR-T Therapy Enabled By Base Editing of Lck to Resist Dasatinib Used to Prevent Rejection Mediated through Both T and NK in Host (ASH 2022) - "Although many strategies, such as clearance of host T/NK cells with alemtuzumab and knockout of B2M gene, have been developed and tested with some success in patients, novel ways to circumvent the surveillance of the host immune system against allogeneic UCAR-T cells are still under intensive investigation...The T315I mutation of ABL kinase is the most prevalent mutation in imatinib resistant patients without affecting its kinase function...Furthermore, dasatinib had no effect on the proliferation of T and NK cell, implying that the immune function can be quickly restored after withdrawing. Allogeneic CAR-T cells have the potential to overcome the limitations of autologous CAR-T cells and Km UCAR-T cells will be a new orthogonal approach that can be combined with other strategies to achieve the goal."

IO biomarker • Hematological Disorders • Hematological Malignancies • Oncology • B2M • CD19 • CD28 • CD69 • IL2RA • LCK