Silencing Fc Domains in T cell-Engaging Bispecific Antibodies Improves T-cell Trafficking and Antitumor Potency.

ABSTRACT: Bispecific antibodies (BsAb) that engage T cells bind to tumor cells via a tumor-associated antigen and to T cells through surface CD3. BsAbs have promising antitumor properties in vivo Here, we describe the effects of Fc silencing on BsAb-driven T-cell trafficking to solid tumors. We used BsAbs specific for disialoganglioside GD2 or oncoprotein ErbB2 (HER2) and built on the IgG(L)-scFv platform with or without Fc silencing. We studied the kinetics of T-cell infiltration from blood into solid tumor masses when driven by these BsAbs. We also investigated the therapeutic efficacy of these BsAbs in two mouse models: immunodeficient mice xenografted with patient-derived GD2⁺ neuroblastoma or HER2⁺ breast cancer, and human CD3ε transgenic mice implanted with a GD2

SUBMITTER: Wang L 

PROVIDER: S-EPMC7398503 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature