Mechanisms of resistance to CAR-T cell immunotherapy: Insights from a mathematical model

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art_SANTURIO_Mechanisms_of_resistance_to_CART_cell_immunotherapy_Insights_2024.PDF (3.01 MB)
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0
Tipo de produção
article
Data de publicação
2024
DOI
Scopus
Web of Science
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE INC
Autores
SANTURIO, Daniela Silva
PAIXAO, Emanuelle A.
ALMEIDA, Regina C.
FASSONI, Artur C.
Citação
APPLIED MATHEMATICAL MODELLING, v.125, p.1-15, 2024
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Chimeric Antigen Receptor (CAR)-T cell therapy long-term follow-up studies revealed nondurable remissions in a significant number of patients. Some of the mechanisms underlying these relapses include poor CAR T cell cytotoxicity or persistence, as well as antigen loss or lineage switching in tumor cells. In order to investigate how antigen-mediated resistance mechanisms affect therapy outcomes, we develop a mathematical model based on a set of integral-partial differential equations. Using a continuous variable to describe the level of antigen expression of tumor cells, we recapitulated important cellular mechanisms across patients with different therapeutic responses. Fitted with clinical data, the model successfully captured the dynamics of tumor and CAR-T cells for several hematological cancers. Furthermore, the role played by these mechanisms are explored with regard to different biological scenarios, such as pre-existing or aquired mutations, providing a deeper understanding of key factors underlying resistance to CAR-T cell immunotherapy.
Palavras-chave
Antigen density, CAR-T therapy, Antigen-positive relapse, Antigen-negative relapse, Mutation, Temporary antigen loss
URI
https://observatorio.fm.usp.br/handle/OPI/57649
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Coleções
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - ODS/03