| Texto completo | |
| Autor(es): |
de Campos, Najla Santos Pacheco
;
Pivetta, Renata Schmieder
;
de Souza, Laura Libanio
;
Kinker, Gabriela Sarti
;
da Silva Medina, Tiago
;
Rodrigues, Tiago
;
Suarez, Eloah Rabello
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | CURRENT TOPICS IN MEDICINAL CHEMISTRY; v. N/A, p. 13-pg., 2025-06-27. |
| Resumo | |
Background Clear cell renal cell carcinoma (ccRCC) is the most prevalent of renal cancers, with a 5-year survival rate of less than 10% for metastatic cases. The most efficient current strategies to treat ccRCC in advanced settings slightly increase progression-free survival. Chimeric antigen receptor T cells (CAR T cells) targeting carbonic anhydrase IX (CAIX) have reemerged as a promising alternative to ccRCC treatment based on recent preclinical data. CAIX and cyclooxygenase-2 (COX-2) are key players in tumor progression across various malignancies, overexpressed in 95% and 50% of ccRCC cases, respectively.Methods This study employed in silico analysis to examine the expression of CAIX and COX-2 in ccRCC cell lines. The effects of celecoxib, anti-CAIX monoclonal antibodies, and anti-CAIX CAR T cells were evaluated using immunofluorescence microscopy and flow cytometry techniques.Results Herein, we show a positive correlation between CAIX and COX-2 expression in ccRCC cell lines in vitro and in silico. Notably, COX-2 blockade with celecoxib led to a significant downregulation of CAIX expression in ccRCC cell lines. This effect is retroactive since treatment of these ccRCC cells with two different anti-CAIX monoclonal antibodies (mAbs) resulted in the downregulation of COX-2 expression. The association of celecoxib with anti-CAIX CAR T cell therapy impaired their cytotoxic potential over ccRCC in vitro, depending on CAIX cellular density.Conclusion These findings suggest a regulatory interaction between CAIX and COX-2 levels, indicating that COX-2 inhibitors may diminish the efficacy of CAIX-targeted therapies and should be avoided in combination treatments. (AU) | |
| Processo FAPESP: | 23/03631-3 - Potencializando a infiltração e funcionalidade de linfócitos T CAR em tumores sólidos por modulação de integrinas |
| Beneficiário: | Eloah Rabello Suarez |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 18/17656-0 - Imunoterapia de nova geração - Direcionamento de linfócitos contendo receptores quiméricos para o combate ao câncer e bloqueio do checkpoint imunológico: eficácia terapêutica e estudos moleculares de mecanismos de exaustão de linfócitos. |
| Beneficiário: | Eloah Rabello Suarez |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 23/00925-6 - Otimização da Função e Infiltração de Linfócitos CAR T no Tratamento de Carcinomas Renais |
| Beneficiário: | Najla Santos Pacheco de Campos |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |