Nucleus of Cellular Therapy - NuTeC

• Grant number: 20/07055-9
• Support Opportunities: Research Grants - Problem-Oriented Research Centers in São Paulo
• Start date: August 01, 2021
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Rodrigo do Tocantins Calado de Saloma Rodrigues
• Grantee: Rodrigo do Tocantins Calado de Saloma Rodrigues
• Host Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Ribeirão Preto , SP, Brazil
• City of the host institution: Ribeirão Preto
• Principal investigators: Eduardo Magalhães Rego ; Raul Machado Neto ; Vanderson Geraldo Rocha ; Virginia Picanço e Castro
• Principal investigators: Kamilla Swiech Antonietto ; Rodrigo do Tocantins Calado de Saloma Rodrigues
• Associated researchers: Adriano Alves Ferreira ; Amanda Mizukami Martins ; Benedito de Pina Almeida Prado Júnior ; Cristiano Gonçalves Pereira ; Gil Cunha De Santis ; Kamilla Swiech Antonietto ; Lucas Eduardo Botelho de Souza ; Maristela Delgado Orellana ; Sandra Coccuzzo Sampaio Vessoni
• Associated scholarship(s): 25/20939-7 - Metabolic enhancement of anti-GD2 CAR-T cells with short-chain fatty acids to boost antitumor activity, BP.IC; 24/04615-4 - Evaluation of a new gene transfer strategy without cell activation for the production of CAR-T cells with higher antineoplastic potential, BP.MS; 23/09711-9 - Use of anti-CD19 CAR-NK cells expressing IL-15/IL-15R± and IL-27 cytokines as an allogeneic treatment for B-cell cancers, BP.DR; + associated scholarships 24/01305-4 - Development of integrated strategies for lentiviral particles purification, BP.MS; 22/16140-5 - Generation of metabolically active NK cells, knockout for the Cish gene, and establishment of non-viral gene transfer strategies for the generation of CAR NK cells (Off-the-shelf)., BP.PD; 23/10187-2 - Somatic mutation profile in lymphocytes of patients with CTLA4 deficiency, BP.IC; 23/06646-1 - Scaling up for preclinical study of hematopoietic stem cells from patients with Immune Aplastic Anemia expanded with UM171, BP.PD; 22/13495-7 - Development of anti-CD19-CAR specific for NK cells to enhance antitumoral effects for the treatment of leukemia and lymphoma., BP.DR; 21/10530-3 - Evaluation of the therapeutic efficacy of anti-GD2 CAR-NK cells with GITRL expression in vitro and in vivo models of tumors of neuroectodermal origin, BP.DR - associated scholarships

Abstract

The Nucleus of Cellular Therapy - NuTeC will be founded on the union of the Regional Blood Center of Ribeirão Preto (Hemocentro RP) and Butantan. Hemocentro RP expertise in cellular therapy will be added to Butantan excellence in the development and production of health applied products to develop CAR T cell therapy. The activities to be conducted by NuTeC are aligned with the scope of this call for the formation of a Problem-oriented Research Nucleus, in the health theme area, focusing on the research line on advanced therapies. NuTeC general objective is to make this promising therapy available to a greater number of patients. Therefore, it will be necessary to scale up and optimize the process of CAR T cell production. Among the specific aims of this proposal we include: I) Scaling up anti-CD19 CAR T cell production according to good manufacture practices (GMP) for treating a large number of patients with CD19+ lymphoid neoplasias; II) Expanding the scale of production of viral vectors in GMP; III) Developing innovative immunotherapies based on the allogeneic transplantation of universal CAR T cells (U-CAR) or NK cells, expressing chimeric receptors against tumor cells; IV) Implementing new vectors in the process of CAR T cell generation that might result in patents for application in other tumor types and obtaining higher safety profile products; and V) Knowledge exchange between participating institutions. Thus, this project will allow the implementation of large-scale CAR T production in Brazil for the treatment of patients with (CD19+) hematological neoplasias. Moreover, the same production platform might be used for CARs designed to other targets that may be used for treating other hematological neoplasias, as well as solid tumors. The results of this project will enable the appropriate production for the safe and effective use of CAR T cells in cancer immunotherapy. (AU)

Scientific publications

(9)

(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)

PICANCO-CASTRO, VIRGINIA; BONAMINO, MARTIN HERNAN; RAMOS, RODRIGO NALIO; GUERINO-CUNHA, RENATO L.; OLIVEIRA, THEO GREMEN M.; REGO, EDUARDO M.. Associacao Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. VIII: CAR-T cells: preclinical development - Safety and efficacy evaluation. Hematology, Transfusion and Cell Therapy, v. 43, n. 2, p. S54-S63, NOV 2021. (19/25309-0, 20/07055-9, 13/08135-2)

SILVESTRE, R. N.; EITLER, J.; DE AZEVEDO, J. T. TEIXEIRA COTTAS; TONN, T.; PICANCO-CASTRO, V.. CD19-CAR NK CELLS CO-EXPRESSING IL15/IL15R alpha SHOW ENHANCED CYTOTOXICITY AGAINST B-CELL LEUKEMIA. CYTOTHERAPY, v. 24, n. 5, p. 2-pg., 2022-05-01. (19/25309-0, 20/08279-8, 13/08135-2, 20/07055-9)

TIRAPELLE, M. C.; SCHMIDT, D. D.; EBRAHIMABADI, S.; COVAS, D.; PICANCO-CASTRO, V.. GD2-TARGETING CAR-NK CELLS ENHANCED BY TRANSGENIC GITRL EXPRESSION ARE AN EFFECTIVE FOR GLIOBLASTOMA AND MELANOMA. CYTOTHERAPY, v. 26, n. 6, p. 1-pg., 2024-06-01. (13/08135-2, 14/50947-7, 20/07055-9, 21/10530-3)

ROS, FELIPE AUGUSTO; COUTO, SAMUEL CAMPANELLI FREITAS; MILHOMENS, JONATHAN; OVIDER, IAN; MAIO, KARINA TOZATTO; JENNIFER, VIVIANE; RAMOS, RODRIGO NALIO; PICANCO-CASTRO, VIRGINIA; KASHIMA, SIMONE; CALADO, RODRIGO T.; et al. A systematic review of clinical trials for gene therapies for ,B-hemoglobinopathy around the world. CYTOTHERAPY, v. 25, n. 12, p. 7-pg., 2023-11-17. (13/08135-2, 20/07055-9, 22/07503-7)

BIGGI, ALISON FELIPE BORDINI; SILVESTRE, RENATA NACASAKI; TIRAPELLE, MARIANE CARIATI; DE AZEVEDO, JULIA TEIXEIRA COTTAS; GARCIA, HENRY DAVID MOGOLLO; DOS SANTOS, MATHEUS HENRIQUE; DE LIMA, SARAH CAROLINE GOMES; DE SOUZA, LUCAS EDUARDO BOTELHO; COVAS, DIMAS TADEU; MALMEGRIM, KELEN CRISTINA RIBEIRO; et al. IL-27-engineered CAR.19-NK-92 cells exhibit enhanced therapeutic efficacy. CYTOTHERAPY, v. 26, n. 11, p. 11-pg., 2024-10-11. (13/08135-2, 19/25309-0, 20/08279-8, 20/07055-9)

BIGGI, A. F.; SILVESTRE, R. N.; TIRAPELLE, M. C.; DE AZEVEDO, J. T.; COVAS, D.; MALMEGRIM, K. C.; FIGUEIREDO, M. L.; PICANCO-CASTRO, V.. IL-27 IN A FOURTH GENERATION CAR ENHANCES CAR-NK CELL EFFECTOR FUNCTION. CYTOTHERAPY, v. 26, n. 6, p. 1-pg., 2024-06-01. (13/08135-2, 14/50947-7, 20/07055-9)

TEIXEIRA COTTAS DE AZEVEDO, J. T.; SILVESTRE, R. N.; COVAS, D.; PICANCO-CASTRO, V.. CD3Z-2B4 INTRACELLULAR DOMAIN IMPROVES CYTOTOXICITY FUNCTION OF CAR-NK CELLS AGAINST CD19+CELL LINES. CYTOTHERAPY, v. 24, n. 5, p. 1-pg., 2022-05-01. (19/25309-0, 20/08279-8, 13/08135-2, 20/07055-9)

DOS SANTOS, M. H.; DE AZEVEDO, J. T.; SILVESTRE, R. N.; RODRIGUES, R. D. DE SALOMA; COVAS, D. T.; PICANCO-CASTRO, V.. INCORPORATION OF 2B4 SIGNALING DOMAIN IN ANTI-CD19 NK-SPECIFIC CARS INCREASES THE POTENCY OF EFFECTOR FUNCTIONS OF CAR-NK CELLS AGAINST MALIGNANT CD19+CELL LINES. CYTOTHERAPY, v. 25, n. 6, p. 1-pg., 2023-06-01. (20/07055-9)

SILVESTRE, RENATA NACASAKI; EITLER, JIRI; DE AZEVEDO, JULIA TEIXEIRA COTTAS; TIRAPELLE, MARIANE CARIATI; FANTACINI, DAIANNE MACIELY CARVALHO; DE SOUZA, LUCAS EDUARDO BOTELHO; SWIECH, KAMILLA; COVAS, DIMAS TADEU; CALADO, RODRIGO T.; MONTERO, PAOLA ORTIZ; et al. Engineering NK-CAR.19 cells with the IL-15/IL-15Rα complex improved proliferation and anti-tumor effect in vivo. FRONTIERS IN IMMUNOLOGY, v. 14, p. 15-pg., 2023-09-25. (13/08135-2, 19/25309-0, 20/08279-8, 20/07055-9)