RT Journal Article T1 Bispecific Antibody Format and the Organization of Immunological Synapses in T Cell-Redirecting Strategies for Cancer Immunotherapy A1 Carrasco Padilla, Carlos A1 Hernaiz Esteban, Alicia A1 Álvarez Vallina, Luis A1 Aguilar Sopeña, Óscar A1 Roda Navarro, Pedro AB 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. PB MDPI SN 1999-4923 YR 2022 FD 2022-12-30 LK https://hdl.handle.net/20.500.14352/72336 UL https://hdl.handle.net/20.500.14352/72336 LA eng NO Ministerio de Ciencia e Innovación (España) NO Instituto de Salud Carlos III NO Fundación CRIS del Cáncer NO Asociación Española Contra el Cáncer NO Fundación “La Caixa” NO Fundación de Investigación Biomédica 12 de Octubre DS Docta Complutense RD 7 jul 2025