Abstract
Immune based therapeutics such as checkpoint inhibitors have proven to work across several cancer types and the potential impact novel immuno-oncology targets can have on inducing anti-cancer responses, either as standalone, or as combination/adjuvant therapies is great. Thus, our central overriding scientific focus is to discover and validate immunoregulatory targets with the potential to induce strong anti-cancer responses. Through establishment of the Center for Research in Immuno-Oncology (CRIO) we will: 1) implement a multidisciplinary research program for discovery and validation of immuno-oncology based targets through a team of subject matter specialists, at A.C.Camargo Cancer Center and Ribeirão Preto Medical School at the University of São Paulo along with other national and international partners, 2) create a technology transfer platform led by researchers and technology transfer attorneys, for advancing the most promising candidates, and 3) implement a robust education and societal knowledge transfer program, led by education and communication specialists. Our goal is to deliver several preclinically validated novel immuno-oncology based targets through the implementation of a range of multidisciplinary approaches. To achieve this goal, CRIO will be composed of 5 working plans (WPs). 1) WP1- is a mechanism-based target identification that aims to establish comprehensive in vitro and in vivo studies to select novel targets for improving the anti-tumor response. The WP1 will be developed into two investigative fronts: A) Targeting immune cells to drive anti-tumor immune responses with a focus on modulation of signaling pathways and epigenetic factors of tumor-associated macrophages, Tregs, neutrophils and CD8 T and B cells) Targeting tumor cells to drive antitumor immune response with a focus on exploring the SWI/SNF complex and inhibitory steroidogenic enzymes modulation. 2) WP2- is an unbiased multi-omics target identification strategy with a focus on discovering novel immuno-modulatory targets in genetic animal models and in prospective and retrospective cohorts of colon, lung and oral cavity cancer patients. 3) WP3 - is the validation phase where the target leads identified in WP1 and WP2 will be confirmed through in vitro and in vivo next-generation preclinical model systems. WP4 - is transfer of technology - CRIO will implement a technology transfer plan designed to move promising candidates forward to the pharmaceutical sector in consultation with GSK and the Center's partner institutions. The CRIO will also dedicate efforts to promote education and knowledge dissemination through implementation of WP5. These will focus at the high school, undergraduate and graduate levels, as well as through creating greater public awareness. This project uses an innovative approach for driving physiologically relevant target discovery using powerful animal models and patient cohorts, followed by validation stages using screening assays of tumor and immune cells under in vitro (organoid, microchips) and in vivo (human PDX-immune reconstituted mice, syngeneic and spontaneous tumor mouse models and Cre/LoxP mice) conditions to best prove anti-tumor activity. This breadth of novel multidisciplinary approaches, aligned with a common theme of immunoregulatory target discovery will provide new opportunities for cancer patients. (AU)
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