Reversal of Endothelial Cell Anergy by T Cell-Engaging Bispecific Antibodies.

ABSTRACT: Objectives: Reduced expression of adhesion molecules in tumor vasculature can limit infiltration of effector T cells. To improve T cell adhesion to tumor endothelial cell (EC) antigens and enhance transendothelial migration, we developed bispecific, T-cell engaging antibodies (bsAb) that activate T cells after cross-linking with EC cell surface antigens. Methods: Recombinant T-cell stimulatory anti-VEGFR2-anti-CD3 and costimulatory anti-TIE2-anti-CD28 or anti-PD-L1-anti-CD28 bsAb were engineered and expressed. Primary lines of human umbilical vein endothelial cells (HUVEC) that constitutively express VEGFR2 and TIE2 growth factor receptors and PD-L1, but very low levels of adhesion molecules, served as models for anergic tumor EC. Results: In cocultures with HUVEC, ant

SUBMITTER: Goncalves M 

PROVIDER: S-EPMC11674949 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature