Strategies to enhance the potential and function of CAR-T cells for therapeutic applications

• Grant number: 17/15840-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2018
• End date: July 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Dimas Tadeu Covas
• Grantee: Amanda Mizukami Martins
• Supervisor: Michael C. Jensen
• Host Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Washington, United States
• Associated to the scholarship: 16/19741-9 - Establishment of a bioprocess for functional CAR-T cell expansion: new frontier for the cancer treatment, BP.PD

Abstract

The treatment of cancer patients with autologous T cells expressing a chimeric antigen receptor (CAR) is one of the most promising adoptive cellular therapy approaches. Although CAR-T cell therapy has demonstrated encouraging results with complete response rates of 70%-90% in patients with B cell malignancies, this new therapeutic modality is not yet fully mastered nor optimized. Some recent data suggest that the infusion of less-differentiated CAR-T cells into the patient conveys superior antitumour efficacy relative to terminally differentiated effector cells. Thus, finding strategies to enrich and expand these primitive T cell subsets is pivotal to ensure efficient T cell expansion and potentially long-term engraftment. In this context, the main objective of this work is to examine the ability of media supplementation to slow the differentiation of T-cells during culture, therefore enhancing the potential of CAR-T cells for therapeutic use. These tests will be performed in small-scale using 24-well G-rex plates and the optimized conditions will be validated on a large scale using G-Rex (closed-system). The strategy of retaining minimally differentiated T cells phenotypes could not only increase safety, antitumour efficacy and reproducibility, but also decrease the CAR-T cell dose and hence the scale of production. Streamlining the process to augment performance while reducing scale could also diminish costs, facilitating the CAR-T cell commercialization.