Cytokines as an important player in the context of CAR-T cell therapy for cancer: Their role in tumor immunomodulation, manufacture, and clinical implications

Author(s)

Farina Silveira, Caio Raony ; Corveloni, Amanda Cristina ; Caruso, Samia Rigotto ; Macedo, Nathalia Araujo ; Brussolo, Natalia Moscheta ; Haddad, Felipe ; Fernandes, Taisa Risque ; de Andrade, Pamela Viani ; Orellana, Maristela Delgado ; Guerino-Cunha, Renato Luiz

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 13, p. 13-pg., 2022-09-12.

Abstract

CAR-T cell therapies have been recognized as one of the most advanced and efficient strategies to treat patients with hematologic malignancies. However, similar results have not been observed for the treatment of solid tumors. One of the explanations is the fact that tumors have extremely hostile microenvironments for the infiltration and effector activity of T-cells, mainly due to the presence of highly suppressive cytokines, hypoxia, and reactive oxygen species. Taking advantage of cytokines functionally, new fourth-generation CAR constructs have been developed to target tumor cells and additionally release cytokines that can contribute to the cytotoxicity of T-cells. The manufacturing process, including the use of cytokines in the expansion and differentiation of T cells, is also discussed. Finally, the clinical aspects and the influence of cytokines on the clinical condition of patients, such as cytokine release syndrome, who receive treatment with CAR-T cells are addressed. Therefore, this review aims to highlight how important cytokines are as one of the major players of cell therapy. (AU)

• FAPESP's process: 20/10804-3 - Development and validation of anti-BCMA CAR-T cells with memory profile for Multiple Myeloma treatment
• Grantee: Caio Raony Farina Silveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral