EXAME DE QUALIFICAÇÃO: Mathematical Modeling of CAR-T Cell Immuno Therapy

Orientadores:
Regina Célia Cerqueira de Almeida - Laboratório Nacional de Computação Científica - LNCC
Luciana Rodrigues Carvalho Barros
Artur Fassoni - Universidade Federal de Itajubá

Banca Examinadora:
João Nisan Correia Guerreiro - Laboratório Nacional de Computação Científica - LNCC (presidente)
Sandra Mara Cardoso Malta - Laboratório Nacional de Computação Científica - LNCC
Luciane Prioli Ciapina - Laboratório Nacional de Computação Científica - LNCC
Martin Hernan Bonamino
Hyun Mo Yang - UNICAMP - UNICAMP

Resumo:

Chimeric Antigen Receptor (CAR)-T cell immunotherapy represents a great advance in the fight against cancer. This therapy aims to increase the ability of T lymphocytes to recognize tumor cells that express specific antigens. This improvement is due to the genetic modification of these cells, through the insertion of the antigen-specific CAR gene. Despite expressive complete response rates, many patients still suffer a relapse and/or become resistant to therapy within the first few years. These barriers that prevent the effective success of the therapy are not completely understood but are related to patient-specific heterogeneity and antigen escape, among other issues. In this research project, the main focus is to study CAR-T immunotherapy responses against hematological cancers. Specifically, we consider patients with Acute Lymphoblastic Leukemia (ALL) and we will study their responses to the CAR-T therapy in the presence of patient-specific heterogeneity and the emergence of innovations in CAR-T constructions. Thus, our goal is to develop mathematical models for both immunodeficient mice and patients, contributing to the advancement of preclinical and clinical research. In this way, our developments can be used as accessory tools for in silico experiments that can contribute to optimizing experimental research. A step towards this aim has been accomplished by developing the CARTmath, an in silico platform for preclinical studies. Overall, the developed models may help to shed light on the structure of the treatment and better understanding the chal - lenges that remain in the study of CAR-T cell immunotherapy.