An affinity-modulated T cell engager targeting Claudin 18.2 shows potent anti-tumor activity with limited cytokine release.

ABSTRACT:

Background

AZD5863 is a bispecific T cell engager (TCE) with high affinity to CLDN18.2 and low affinity to cluster of differentiation 3 (CD3), designed to decrease its peripheral cytokine release potential, improve the therapeutic index, and maintain potent anti-tumor activity.

Methods

AZD5863 was evaluated using CLDN18.2-expressing human cell lines alone or in co-cultures with human or cynomolgus monkey peripheral blood mononuclear cells to determine affinities, specificity, potency, and bystander killing activity. In vivo, AZD5863-mediated tumor growth inhibition and pharmacodynamics were evaluated in humanized mice or human CD3 transgenic mice implanted with CLDN18.2-expressing cancer cell lines.

Results

AZD5863 was shown to bind specifically to human and cynomolgu

SUBMITTER: Gaspar M 

PROVIDER: S-EPMC12323529 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature