Unbiased discovery of antibody therapies that stimulate macrophage-mediated destruction of B-cell lymphoma.

ABSTRACT: Macrophages are critical effectors of antibody therapies for lymphoma, but the best targets for this purpose remain unknown. Here, we sought to define a comprehensive repertoire of cell surface antigens that can be targeted to stimulate macrophage-mediated destruction of B-cell lymphoma. We developed a high-throughput assay to screen hundreds of antibodies for their ability to provoke macrophages to attack B-cell lymphoma cells. Across both mouse and human systems, we identified multiple unappreciated targets of opsonization as well as putative immune checkpoints. We used this information to engineer a compendium of 156 bispecific antibodies, and we identified dozens of bispecifics that dramatically stimulate macrophage-mediated cytotoxicity of lymphoma cells. Among these, a bispecific com

SUBMITTER: Ribeiro J 

PROVIDER: S-EPMC11601295 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature