Doer Bio published pre-clinical research results of the trispecific antibody DR30318 in Cancer Immunology, Immunotherapy


On March 31, 2024, pre-clinical research results of the tri-specific antibody DR30318 independently developed by Zhejiang Doer Biologics Co., Ltd. (Doer Bio), were published in Cancer Immunology,Immunotherapy, an high-impact journal in the field of tumor immunotherapy (2022 JCR lmpact Factor impact factor 5.8, 5-year impact factor 6.1). The article is entitled "DR30318, a novel tri-specific T cell engager for Claudin 18.2 positive cancers immunotherapy". Dr. Yanshan Huang, Founder /CEO of Zhejiang Doer Biologics, and Professor Lushan Yu, Institute of Pharmaceutical Analysis, School of Pharmacy, Zhejiang University, are co-corresponding authors of this paper.

Claudin 18.2 is one of the subtypes of Claudin 18. Its expression in normal tissues is limited to differentiated gastric epithelial cells, while it is highly expressed in gastric cancer, pancreatic cancer, esophageal cancer and other cancers, showing good tissue-specific and targetable properties.

Based on the SMART-VHHBody and MultipleBody technology platforms independently developed by Doer Bio, a single domain antibody specifically targeting Claudin18.2 was screened and obtained, and was fused to antibodies against human serum albumin (HSA) and CD3 to construct a tri-specific fusion protein (DR30318) that can specifically target Claudin18.2 with a prolonged half-life and tumor killing activity. Results of preclinical studies showed that DR30318 can specifically binds to the targets, and showed good pharmacokinetic characteristics in mice and cynomolgus monkeys. In vitro killing assays showed that DR30318 exhibited a high T-cell-mediated cytotoxicity (TDCC), especially in low Claudin 18.2-expressed tumor cell lines. In xenograft tumor model experiments, DR30318 completely inhibited the growth of tumor cells. In cytokine release tests, DR30318-mediated cytokine release depends on the presence of target cells, which shows good safety characteristics and clinically developing prospects.

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