Combining mathematical modeling, <i>in vitro</i> data and clinical target expression to support bispecific antibody binding affinity selection: a case example with FAP-4-1BBL.

ABSTRACT: The majority of bispecific costimulatory antibodies in cancer immunotherapy are capable of exerting tumor-specific T-cell activation by simultaneously engaging both tumor-associated targets and costimulatory receptors expressed by T cells. The amount of trimeric complex formed when the bispecific antibody is bound simultaneously to the T cell receptor and the tumor-associated target follows a bell-shaped curve with increasing bispecific antibody exposure/dose. The shape of the curve is determined by the binding affinities of the bispecific antibody to its two targets and target expression. Here, using the case example of FAP-4-1BBL, a fibroblast activation protein alpha (FAP)-directed 4-1BB (CD137) costimulator, the impact of FAP-binding affinity on trimeric complex formation and pharmacol

SUBMITTER: Sanchez J 

PROVIDER: S-EPMC11497128 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature