Carrasco-Padilla Carlos, Hernaiz-Esteban Alicia, Álvarez-Vallina Luis, Aguilar-Sopeña Oscar, Roda-Navarro Pedro
Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid and 12 de Octubre Health Research Institute (imas12), 28040 Madrid, Spain.
Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario 12 de Octubre, 28009 Madrid, Spain.
Pharmaceutics. 2022 Dec 30;15(1):132. doi: 10.3390/pharmaceutics15010132.
T cell-redirecting strategies have emerged as effective cancer immunotherapy approaches. Bispecific antibodies (bsAbs) are designed to specifically recruit T cells to the tumor microenvironment and induce the assembly of the immunological synapse (IS) between T cells and cancer cells or antigen-presenting cells. The way that the quality of the IS might predict the effectiveness of T cell-redirecting strategies, including those mediated by bsAbs or by chimeric antigen receptors (CAR)-T cells, is currently under discussion. Here we review the organization of the canonical IS assembled during natural antigenic stimulation through the T cell receptor (TCR) and to what extent different bsAbs induce T cell activation, canonical IS organization, and effector function. Then, we discuss how the biochemical parameters of different formats of bsAbs affect the effectivity of generating an antigen-induced canonical IS. Finally, the quality of the IS assembled by bsAbs and monoclonal antibodies or CAR-T cells are compared, and strategies to improve bsAb-mediated T cell-redirecting strategies are discussed.
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