Directed protein engineering identifies a human TIM-4 blocking antibody that enhances anti-tumor response to checkpoint inhibition in murine colon carcinoma.

ABSTRACT:

Background

T-cell immunoglobulin and mucin domain containing molecule-4 (TIM-4) is a scavenger receptor best known for its role in recognizing dying cells. TIM-4 orchestrates phagocytosis allowing for cellular clearance of apoptotic cells, termed efferocytosis. It was previously shown that TIM-4 directly interacts with AMPKα1, activating the autophagy pathway, leading to degradation of ingested tumors, and effectively reducing antigen presentation.

Methods

This study sought to identify a novel human TIM-4 antibody that can prevent phagocytosis of tumor cells thereby allowing for more antigen presentation resulting in anti-tumor immunological response. Using phage display panning directed against human TIM-4, we engineered a novel human TIM-4 antibody (SKWX301). Combination o

SUBMITTER: Frietze KK 

PROVIDER: S-EPMC11638112 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature