Immune Oncology

IMMUNE ONCOLOGY PROGRAM PROJECT SUMMARY/ABSTRACT The objectives of the Immune Oncology (IO) Program are to improve cancer diagnosis, care and cure rates through better understanding of molecular and cellular interplay between cancer cells and the immune system and optimizing the efficacy of cellular and molecular immunotherapies and stem cell transplantation (SCT). Program members investigate the roles of immune and cellular processes in health and disease, discover the contribution of host-derived genetic and molecular contributors to immune evasion, overcome mechanisms of resistance and tolerance to immune therapies by cancer cells, improve current and new roles of innate and adaptive immunity in immune responses to both liquid and solid cancers, and create a portfolio of translational application focusing toward developing new cell-based and immune-modulating treatments for both solid tumors and hematological malignancies. The program is organized around 3 scientific aims: 1) Elucidate the genetic and molecular mechanisms that control antitumor immunity and recognition of cancer cells by immune cells 2) Discover novel strategies to overcome acquired and/or adaptive immune resistance to adoptive cell therapy, tumor vaccines, immune checkpoint blockade and other immune-based approaches 3) Develop clinical trials leveraging novel molecular, cellular and immune cancer therapeutics, such as cell-based therapies, hematopoietic SCT and small molecule immune modulators. These aims reflect major working groups and initiatives that coalesces program members with other cancer center investigators through inter-programmatic collaborations that result in preclinical and clinical research efforts, grants, and trial protocols. Extensive use of an array of shared resources, in particular, Genomics, Hematopoietic, Cytometry, Biostatistics, Tissue, and Translational Research facilitate all aspects of member discoveries. Under the leadership of Timothy Chan (Co- Leader), David Wald (Co-Leader) and Alex Huang (Co-Leader) the IO Program has 48 full members representing 11 different departments across all 3 consortium institutions. Members are funded with a total of $14.7M in grant funding (annual direct costs), of which $7.3M is peer-reviewed and $4.4M is NCI-funded. During the last funding period, IO program members published 1,194 cancer-focused publications. Cancer and program related publications included 34% inter-programmatic and 25% intra-programmatic publications. This highly effective program has made major practice-changing contributions benefiting cancer patients. Examples include: the discovery of POLE/D1 functional mutations that impact sensitivity to immune checkpoint blockade, the clinical translation of multiple novel cell therapy products including a BAFF CAR-T product and ultra-fast (<1 day manufacturing) CAR-T products for myeloma and lymphoma, and the clinical translation of multiple approaches to target TGF-beta in cancer including a multi-center international clinical trial for pediatric osteosarcoma.