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SELECTBIO Conferences Cell & Gene Therapy Asia 2019


Current Status and Future Directions of CAR-T Cell Therapy

Keiya Ozawa, Professor Emeritus and Visiting Professor of the Division of Immuno-Gene & Cell Therapy, Jichi Medical University

Adoptive immunotherapy with CAR (chimeric antigen receptor)-T cells is a promising cell-based anticancer therapy for hematological malignancies. CARs are hybrid proteins consisting of an extracellular single chain fragment of variable region (scFv) fused to intracellular lymphocyte signaling domains CD28 or 4-1BB, coupled with CD3 to mediate T cell activation. CD19-targeted CAR-T cell therapy showed surprising clinical efficacy against relapsed/refractory acute lymphoblastic leukemia and malignant lymphoma. In 2017, this novel treatment was approved by FDA in USA. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and tumor lysis syndrome (TLS) are adverse effects that appear at an early stage following the infusion of CAR-T cells. Delayed onset toxicity of CD19-CAR-T cell therapy is the serum immunoglobulin deficiency due to destruction of normal B cells (on-target, off-tumor reaction). A next promising target antigen is considered to be BCMA (B cell maturation antigen), and BCMA-CAR-T cell therapy has been shown to be effective against multiple myeloma. On the other hand, the efficacy of CAR-T cell therapy for solid tumors has been unclear. There are several issues to be solved, and CAR-T for solid tumors should be combined with other therapeutic technologies. Currently, genome editing technology is rapidly progressing, and its application to gene-modified T cell therapy is being conducted; e.g. 1) TCR gene knockout for allogeneic (universal) CAR-T cell therapy and 2) PD-1 gene knockout of CAR-T cells (immune checkpoint blockade) to increase its cytotoxic activity. Another major issue is that gene therapies recently approved in Europe and the U.S. are extremely expensive.

Add to Calendar ▼2019-11-11 00:00:002019-11-12 00:00:00Europe/LondonCell and Gene Therapy Asia 2019Cell and Gene Therapy Asia 2019 in Kobe, JapanKobe,