Targeting two distinct epitopes on human CD73 with a bispecific antibody improves anticancer activity.

ABSTRACT:

Background

Immunosuppressive extracellular adenosine is generated by the enzymatic activity of CD73. In preclinical models, antibodies (Abs) targeting different epitopes on CD73 exert anticancer activity through distinct mechanisms such as inhibition of enzymatic activity, engagement of Fc receptors, and spatial redistribution of CD73.

Methods

Using controlled Fab arm exchange, we generated biparatopic bispecific antibodies (bsAbs) from parental anti-CD73 Abs with distinct anticancer activities. The resulting anticancer activity was evaluated using in vitro and in vivo models.

Results

We demonstrate that different anticancer activities can be combined in a biparatopic bsAb. Remarkably, the bsAb significantly improved the enzyme inhibitory activity compared with the pa

SUBMITTER: Gammelgaard OL 

PROVIDER: S-EPMC9472124 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature