Anti-BCMA CAR-T Cell Development for Multiple Myeloma Treatment

• Grant number: 25/01498-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Vanderson Geraldo Rocha
• Grantee: Taís Aparecida Matozo de Souza
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID

Abstract

Multiple myeloma (MM) is a B cell neoplasia that accounts for 10% of all hematological tumors. Despite the progress in MM therapies most patients still relapse. CAR-T cell therapy with anti-BCMA (a receptor expressed exclusively by mature B and MM cells), are able to increase patient survival and delay relapses. Although there are some approved CAR-T therapy in agencies such as the FDA, available treatment has a low lifespan, presenting relapses after eight months after cell infusion. Therefore, there is a need to evaluate new CAR constructs that increase T cell efficiency and resistance in patients body, without causing secondary damage. Thus, the aim of this study is to assess the efficiency of a new CAR construct biparatopic anti-BCMA as a potential treatment for MM. To this end, we will transduce MM patient lymphocytes with a lentiviral vector carrying the new CAR anti-BCMA construct. After cell transduction and expansion, CAR expression will be evaluated to assess transduction efficiency by flow cytometry. We will also evaluate lymphocytes subpopulations and exhaustion by the end of cell culture. In addition, cytotoxic potential of lymphocytes will be evaluated by the killing of immortalized MM cells by CAR-T cells. Moreover, we will evaluate the cytokines secreted by CAR-T by ELISA assay. Altogether, we expect this study to be a first step for a clinical study with a more efficient and persistent CAR-T treatment for MM patients.