Immunomodulatory Activity of the Tyrosine Kinase Inhibitor Dasatinib to Elicit NK Cytotoxicity against Cancer, HIV Infection and Aging

Pharmaceutics. 2023 Mar 11;15(3):917. doi: 10.3390/pharmaceutics15030917.

Abstract

Tyrosine kinase inhibitors (TKIs) have been extensively used as a treatment for chronic myeloid leukemia (CML). Dasatinib is a broad-spectrum TKI with off-target effects that give it an immunomodulatory capacity resulting in increased innate immune responses against cancerous cells and viral infected cells. Several studies reported that dasatinib expanded memory-like natural killer (NK) cells and γδ T cells that have been related with increased control of CML after treatment withdrawal. In the HIV infection setting, these innate cells are associated with virus control and protection, suggesting that dasatinib could have a potential role in improving both the CML and HIV outcomes. Moreover, dasatinib could also directly induce apoptosis of senescence cells, being a new potential senolytic drug. Here, we review in depth the current knowledge of virological and immunogenetic factors associated with the development of powerful cytotoxic responses associated with this drug. Besides, we will discuss the potential therapeutic role against CML, HIV infection and aging.

Keywords: CML; CMV; HIV functional cure; HIV-1; anti-aging; cancer; dasatinib; memory-like NK cells; senolytic; tyrosine kinase inhibitors; γδ T cells.

Publication types

  • Review

Grants and funding

This review was partially supported by grants from the “Programa de becas Gilead a la investigación Biomédica GLD21_00111”; “Fondo Europeo para el Desarrollo Regional” (FEDER); the SPANISH AIDS Research Network RD12/0017/0001, RD16/0025/0002 and RD16/0025/0014-ISCIII-FEDER (RIS); the “Fondo de Investigación Sanitaria” (FIS) PI04/0363, PI20/00676; HIVACAT Programme and the CERCA Programme/“Generalitat de Catalunya” SGR 615 and SGR 653. Our group received funding from “la Caixa” Foundation under agreement, as well as from CIBERINFEC from the “Instituto de Salud Carlos III”, Madrid, Spain.