Center for Research in Immuno-Oncology (CRIO)

• Grant number: 21/00408-6
• Support Opportunities: Research Grants - Research Centers in Engineering Program
• Start date: July 01, 2022
• End date: June 30, 2027
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Agreement: GlaxoSmithKline
• Principal Investigator: Kenneth John Gollob
• Grantee: Kenneth John Gollob
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil
• Host Companies: Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE); Glaxosmithkline Brasil Ltda
• City: São PauloRio de Janeiro
• Pesquisadores principais:( Atuais ): Dirce Maria Carraro ; Emmanuel Dias-Neto ; Israel Tojal da Silva
• Pesquisadores principais:( Anteriores ): José Carlos Farias Alves Filho
• Associated researchers: Amanda Braga de Figueiredo ; Ariê Carneiro ; Carlos Wagner de Souza Wanderley ; Celso Abdon Lopes de Mello ; Clóvis Antonio Lopes Pinto ; Diana Noronha Nunes ; Fernando Cotait Maluf ; Fernando de Queiroz Cunha ; Giovana Tardin Torrezan ; Glaucia Noeli Maroso Hajj ; Gustavo Schvartsman ; Helano Carioca Freitas ; Jefferson Luiz Gross ; Joao Bosco de Oliveira Filho ; João Renato Rebello Pinho ; Leandro Machado Colli ; Luiz Paulo Kowalski ; Maria Paula Curado ; Paulo Vidal Campregher ; Pedro Luiz Serrano Uson Junior ; Rachel Simões Pimenta Riechelmann ; Samuel Aguiar Junior ; Sergio Eduardo Alonso Araujo ; Thiago Bueno de Oliveira ; Thiago Mattar Cunha ; Tiago Góss dos Santos ; Vilma Regina Martins
• Associated research grant(s): 24/02226-0 - Abordagens genômicas amplas e análise de DNA tumoral circulante para detecção de biomarcadores preditivos de resposta ao tratamento oncológico com inibidores de checkpoint imunológico, AP.R
• Associated scholarship(s): 24/10964-1 - Multiomic Strategy to Identify Novel Immunomodulatory Targets in Prospective and Retrospective Cohorts of Colorectal Cancer Patients, BP.PD; 25/01476-6 - Characterization of systemic and tumor mechanisms related to treatment failure in patients with lung cancer, BP.PD; 24/13060-6 - Multi-omics strategies with a focus on discovering novel immuno-modulatory targets in prospective and retrospective cohorts of gynaecological cancer patients, BP.PD; + associated scholarships 24/06238-3 - Characterization of soluble biomarkers related to treatment failure in patients with head and neck cancer, BP.TT; 23/09229-2 - Development of multiomic approaches and pipelines to discovery of biomarkers and elucidation of immune mechanisms related to treatment outcome in Cancer patients, BP.PD; 23/07676-1 - Characterization of soluble and cellular biomarkers related to therapeutic failure in patients with cervical cancer, BP.TT; 23/05690-7 - Multi-omics strategies with a focus on discovering novel immuno-modulatory targets in prospective and retrospective cohorts of gynaecological cancer patients, BP.PD; 23/07734-1 - Processing of FFPE tumor samples and evaluation of immune infiltrate by IHC., BP.TT; 22/10585-5 - Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1a) at the interface between mitochondrial activity, regulatory T cell biology and Cancer, BP.PD; 23/00413-5 - Immune targets for improving the anti-tumor response - communication and dissemination plan regarding the targets imuno cancer research, BP.JC; 22/15181-0 - Establishing patient-derived platform to validate putative targets for immunotherapy, BP.PD; 22/16099-5 - Characterization of soluble and cellular biomarkers related to treatment failure in patients with colon cancer, BP.TT; 22/16551-5 - Processing of FFPE tumor samples and evaluation of immune infiltrate by IHC, BP.TT; 22/13887-2 - Development of multiomic approaches and pipelines to discovery of biomarkers and elucidation of immune mechanisms related to treatment outcome in cancer patients, BP.PD; 22/11149-4 - Regulation of cancer-specific immune response by targeting tumor-associated macrophages (TAMs) and regulatory T cells (Tregs), BP.PD; 22/13405-8 - Processing the feces and tumor tissues for microbiota analysis, BP.TT; 22/11151-9 - Exploring the role of neutrophil extracellular traps (NETs) and the SWI/SNF complex in the regulation of the antitumoral immune response, BP.PD - associated scholarships

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE BRITTO EVANGELISTA, GUILHERME FERREIRA; FIGUEIREDO, AMANDA BRAGA; DE BARROS E SILVA, MILTON JOSE; GOLLOB, KENNETH J.. Balancing the good and the bad: controlling immune-related adverse events versus anti-tumor responses in cancer patients treated with immune checkpoint inhibitors. IMMUNOTHERAPY ADVANCES, v. 2, n. 1, p. 8-pg., 2022-05-19. (21/00408-6)

DE ALENCAR, VIVIANE TEIXEIRA L.; FIGUEIREDO, AMANDA B.; CORASSA, MARCELO; GOLLOB, KENNETH J.; DE LIMA, VLADMIR CORDEIRO C.. Lung cancer in never smokers: Tumor immunology and challenges for immunotherapy. FRONTIERS IN IMMUNOLOGY, v. 13, p. 14-pg., 2022-08-24. (21/00408-6)

FIGUEIREDO, AMANDA BRAGA; BARROS E SILVA, MILTON JOSE; DE BRITTO EVANGELISTA, GUILHERME FERREIRA; DE LIMA GALDINO, NAYANE ALVES; DE MELO KUIL, LARISSA; SANTOS, IASMIM POLIDO; MORAIS, KATIA LUCIANO PEREIRA; CAVALCANTI, CLARA MACIEL; MOREDO, LUCIANA FACURE; DUPRAT-NETO, JOAO PEDREIRA; et al. Immune mechanisms and predictive biomarkers related to neoadjuvant immunotherapy response in stage III melanoma. HELIYON, v. 10, n. 12, p. 11-pg., 2024-06-30. (21/00408-6, 18/06409-1)