TUMOR IMMUNOLOGY RESEARCH PROGRAM (TI) ABSTRACT AACR president-elect Antoni Ribas, MD, PhD (Director) together with T cell engineer Yvonne Chen, PhD (Co- Director) lead the UCLA Jonsson Comprehensive Cancer Center (JCCC) Tumor Immunology Research Program (TI). Ribas and Chen stimulate Program cohesion and goal-oriented achievement through two independent but related objectives, which are to provide a highly interactive and supportive environment that deepens member understanding of tumor immunology, and to develop novel immune-based therapies for patients with cancer. TI brings basic and translational scientists together, guided by Los Angeles County (LAC) catchment area needs and priorities, to spawn novel investigator-initiated immunotherapy clinical trials in melanoma, lymphoma, brain, lung, and kidney cancer, and other tumor types. There are many TI Program strengths, including in the following nine areas. (1) Bringing new cancer immunotherapies to drug regulatory approval. (2) Uncovering mechanisms of response and resistance to immune checkpoint blockade. (3) Clinical trials of genetically engineered T cells and their precursors with T cell receptors (TCRs) or chimeric antigen receptors (CARs) to generate cancer- directed immune systems. (4) Non-invasive imaging of tumor antigen-specific T cell distributions and tumor targeting in vivo. (5) Engineering new platforms for immune monitoring of T cell responses to cancer. (6) Examining the relationship between inflammation and cancer. (7) Generating and using antibody fusion proteins for cancer therapy. (8) Investigating therapeutic combinations with targeted agents to sensitize cancer cells to immunotherapy. (9) Studies aiming to improve the lives of patients with AIDS-related cancers. These nine and additional basic and translational Program strengths rely heavily upon a CCSG-funded infrastructure and all six JCCC Shared Resources. The Flow Cytometry Shared Resource (FCSR) is the most active core and the Small Animal Imaging Shared Resource (SAISR) enables T cell imaging projects that move from preclinical models to patients. Outside of the six official JCCC Shared Resources is the JCCC/Human Gene Medicine Program Good Manufacturing Practices (GMP) facility, which TI investigators use to manufacture personalized cell products in- house, meeting local, state, and federal regulations for use in humans. The TI Program has 31 members from 11 departments in four schools at UCLA and affiliate, Caltech. As of March 1, 2019, the Program had $19,280,597 in direct cost funding, including $4,823,507 (25%) from the NCI, and $14,028,565 (73%) in direct cost peer-reviewed funding. Program discoveries resulted in 627 publications, with 13% from intra-programmatic and 37% from inter-programmatic collaborations. In addition, 57% of publications are from collaborations with external institutions and 44% are in high-impact (IF ?10, or field leading) journals. Impactful Program research yielded paradigm shifting discoveries in mechanisms of immunotherapy resistance and practice changing advances with three FDA approvals since 2014, the first FDA approvals for immune checkpoint inhibitors in cancer, for melanoma and lung cancer, and FDA approval for anti-CD19 CAR-T cells in large B cell lymphoma.
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