Lung-Ji Chang

Shenzhen Geno-immune Medical Institute



Title:

CAR-T Therapy Today

Abstract:

Earlier studies based on the CD19 chimeric antigen receptor-modified T cells targeting CD19-positive B cell malignancies have demonstrated improved responses even in very late-stage cancer patients (pts). Still, many experienced relapses and became CART-resistant. To improve this new technology, novel cancer targeting immunotherapy strategies have been developed including identification of neoepitope mutation antigens to overcome cancer escape and tolerance. Results of these novel immunotherapies for hematological malignancies and solid tumors will be presented and discussed.

Pts who have exhausted all conventional treatments with progressive but stable disease and life expectancy >3 months ar e enrolled in the study. Tumor biopsies are immunostained to identify target antigens, or subjected to whole exome sequencing to identify mutations in individual tumor specimens. The choice of immune cell targets is based on strong positive staining results and confirmation from similar disease specimens. Individual MHC-specific cytotoxic T lymphocyte (CTL) are generated based on the best-fit neoepitope binding modeling on pt-specific MHC molecules. Autologous T cells are apheresis collected. CTL are generated in antigen-pulsed dendritic cell coculture.  Chimeric antigen receptor (CAR) T cells are produced using an apoptosis-inducible, safety-engineered lentiviral CAR (4SCAR) with the following intracellular signaling domains: CD28/CD27/CD3ζ-iCasp9. Pts receive cyclophosphamide and/or fludarabine chemotherapy conditioning 1-2 days before infusions of ~1x106 cancer-specific T cells/kg per infusion. The quality of apheresis cells, efficiencies of gene transfer and T cell proliferation is scored, and T cell infusion dose and blood CAR copies are quantitatively determined.

Bio

Dr. Lung-Ji Chang, professor of the School of Medicine and the University of Electronic Science and Technology in Chengdu, President of Shenzhen Geno-Immune Medical Institute in Shenzhen and professor of the Department of Molecular Genetics and Microbiology at the University of Florida. His research is focused on developing innovative gene and cell therapy strategies to investigate the disease mechanisms and clinical translation approaches. The emphasis of his research is to translate basic science into clinical applications. Professor Chang’s research activities include the design of new therapeutic regimes for treating infectious diseases, genetic diseases and cancer, understanding the mechanisms of immune cell development including dendritic cells and T cells from hematopoietic progenitor/stem cells, and exploring translational applications of stem cells.