CD40×HER2 bispecific antibody overcomes the CCL2-induced trastuzumab resistance in HER2-positive gastric cancer.

ABSTRACT:

Background

There was much hard work to study the trastuzumab resistance in HER2-positive gastric cancer (GC), but the information which would reveal this abstruse mechanism is little. In this study, we aimed to investigate the roles of tumor cell-derived CCL2 on trastuzumab resistance and overcome the resistance by treatment with the anti-CD40-scFv-linked anti-HER2 (CD40 ×HER2) bispecific antibody (bsAb).

Methods

We measured the levels of CCL2 expression in HER2-positive GC tissues, and revealed biological functions of tumor cell-derived CCL2 on tumor-associated macrophages (TAMs) and the trastuzumab resistance. Then, we developed CD40 ×HER2 bsAb, and examined the targeting roles on HER2 and CD40, to overcome the trastuzumab resistance without systemic toxicity.

Results</

SUBMITTER: Sun W 

PROVIDER: S-EPMC9295658 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature