DR30318, a novel tri-specific T cell engager for Claudin 18.2 positive cancers immunotherapy

Sep 21, 2026

Claudin 18.2 (CLDN18.2) is presented as a highly anticipated target for solid-tumor treatment, particularly in advanced gastric and pancreatic carcinomas, where current outcomes remain poor. A novel tri-specific T cell engager, DR30318, is developed against CLDN18.2 for gastric and pancreatic immunotherapy, designed to bind CLDN18.2, human serum albumin, and CD3 on T cells. DR30318 shows in vitro TDCC activity, favorable rodent and NHP half-life, and cytokine induction, with significant tumor suppression in CLDN18.2-positive xenograft models.

LanguageEnglish

CategoryHealthcare

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Pages14

Reading Time35 min

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Abstract

Background

Methods

Results

Introduction

Cancer Immunology, Immunotherapy (2024) 73:82 [https://doi.org/10.1007/s00262-024-03673-x](https://doi.org/10.1007/s00262-024-03673-x) DR30318, a novel tri‑specific T cell engager for Claudin 18.2 positive cancers immunotherapy Zhe Ma1,2 · Zhenxing Zhou2 · Wenwen Duan2 · Gaofeng Yao2 · Shimei Sheng2 · Sidou Zong2 · Xin Zhang2 · Changkui Li2 · Yuanyuan Liu2 · Fengting Ou5 · Maha Raja Dahar1 · Yanshan Huang2 · LushanYu1,3,4,5,6 Received: 20 February 2024 / Accepted: 8 March 2024 © The Author(s) 2024 Abstract Background Claudin 18.2 (CLDN18.2) is a highly anticipated target for solid tumor therapy, especially in advanced gastric carcinoma and pancreatic carcinoma. The T cell engager targeting CLDN18.2 represents a compelling strategy for enhancing anti-cancer efficacy. Methods Based on the in-house screened anti-CLDN18.2 VHH, we have developed a novel tri-specific T cell engager targeting CLDN18.2 for gastric and pancreatic cancer immunotherapy. This tri-specific antibody was designed with binding to CLDN18 .2, human serum albumin (HSA) and CD3 on T cells. Results The DR30318 demonstrated binding affinity to CLDN18.2, HSA and CD3, and exhibited T cell-dependent cellular cytotoxicity (TDCC) activity in vitro. Pharmacokinetic analysis revealed a half-life of 22.2–28.6 h in rodents and 41.8 h in cynomolgus monkeys, respectively. The administration of DR30318 resulted in a slight increase in the levels of IL-6 and C-reactive protein (CRP) in cynomolgus monkeys. Furthermore, after incubation with human PBMCs and CLDN18.2 expressing cells, DR30318 induced TDCC activity and the production of interleukin-6 (IL-6) and interferon-gamma (IFN-γ) . Notably, DR30318 demonstrated significant tumor suppression effects on gastric cancer xenograft models NUGC4/ hCLDN18.2 and pancreatic cancer xenograft model BxPC3/hCLDN18.2 without affecting the body weight of mice. Keywords Claudin 18.2 · T cell engager · Gastric cancer · Pancreatic cancer · Cytokines · TDCC Zhe Ma and Zhenxing Zhou have contributed equally to the work. * Yanshan Huang [yanshanhuang@doerbio.com](yanshanhuang@doerbio.com) * Lushan Yu[yuls@zju.edu.cn](yuls@zju.edu.cn) 1 Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang Province, China 2 Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd., Hangzhou 310058, Zhejiang Province, China 3 National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China 4 Department of Pharmacy, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China 5 Jinhua Institute of Zhejiang University, Jinhua 321036, China 6 Department of Pharmacy, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing 312000, China Introduction Gastric cancer, ranked as the sixth most prevalent cancer globally, is the third leading cause of cancer-related mortality [1], and is widely recognized as one of the most challenging malignancies to treat. Although early gastric cancer exhibits a 5-year overall survival rate (OSR) exceeding 90% in Asia [2–5], the OSR for advanced gastric cancer remains low due to late-stage diagnosis in over 80% of patients [6] . Pancreatic cancer is characterized by a dismal prognosis and high mortality, making it the most lethal disease. In 2019, the survival rate of patients diagnosed with pancreatic adenocarcinoma was 24% at 1 year and only 9% at 5 years in the USA and Europe in 2019 [1, 7] . The relatively low survival rate can be partly attributed to the prevalence of advancedstage diagnosis in most cases, as only approximately 20% of patients are diagnosed at an early stage when surgical resection is feasible [8] . Furthermore, even after surgery without additional therapy, more than 90% of patients experience disease relapse and succumb to their illness [9]

FAQs

What is Claudin 18.2 (CLDN18.2) and why is it targeted for therapy?

CLDN18.2 is described as a highly anticipated target for solid tumor therapy, with CLDN18.2 expression being aberrant in multiple cancers such as gastric and pancreatic cancer. Its specific expression pattern supports therapeutic targeting for these malignancies.

How is DR30318 designed and what does it bind to?

DR30318 is a novel tri-specific T cell engager designed to bind CLDN18.2, human serum albumin (HSA), and CD3 on T cells. This design enables coordinated engagement of the target and T-cell activation.

What key preclinical effects were observed for DR30318?

DR30318 demonstrates binding to CLDN18.2, HSA, and CD3 and shows T cell-dependent cellular cytotoxicity (TDCC) in vitro. It induces IL-6 and IFN-γ after incubation with human PBMCs and CLDN18.2-expressing cells, and it significantly suppresses tumor growth in relevant gastric and pancreatic xenograft models without affecting mouse body weight.

Sep 21, 2026

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