Revolutionizing Gastric Cancer Treatment: Targeted Radiotherapy with Zolbetuximab and abinScience Support

Gastric cancer ranks as the fifth most common cancer worldwide, claiming hundreds of thousands of lives each year. Most patients receive a late-stage diagnosis, where traditional chemotherapy often leads to drug resistance and severe side effects. While treatments like chemotherapy, targeted therapies (e.g., trastuzumab), and immunotherapies (e.g., PD-1 inhibitors) are standard, they frequently fall short. A groundbreaking study from the Shanghai Institute of Applied Physics, published in Molecular Pharmaceutics, explores a new approach: combining radiotherapy with monoclonal antibodies using [131I]I-Zolbetuximab to target CLDN18.2-positive gastric cancer, offering a potential paradigm shift in treatment.

Targeted Radiotherapy for Gastric Cancer: The Role of CLDN18.2

CLDN18.2, a tight junction protein in the Claudin family, is overexpressed in gastric cancer, making it a promising therapeutic target. Zolbetuximab, the first monoclonal antibody designed to target CLDN18.2, has shown success in clinical trials, extending survival when paired with chemotherapy like mFOLFOX6. The Shanghai study takes this further by labeling Zolbetuximab with iodine-131 to create [131I]I-Zolbetuximab, a radiolabeled antibody that delivers targeted radiation to kill tumor cells while minimizing systemic toxicity.

How [131I]I-Zolbetuximab Was Developed

Researchers used the Iodogen method to label Zolbetuximab with iodine-131, achieving a labeling efficiency of 96.05% and a specific activity of 1.75×10² GBq/μmol. The radiolabeled antibody maintained over 90% radiochemical purity in PBS and serum after 24 hours, demonstrating robust stability for clinical applications.

Fig. 1 Diagram illustrating the labeling of Zolbetuximab with [131I] using the Iodogen method for targeted radiotherapy in gastric cancer.

Key Findings from the Study

The study evaluated [131I]I-Zolbetuximab in CLDN18.2-positive gastric cancer models, yielding promising results:

Fig. 2 Bar graphs showing endocytosis, surface-bound, and cell-retained [131I]I-Zolbetuximab in MKN45-CLDN18.2 cells over 24 hours.

Fig. 3 Immunohistochemistry images showing CLDN18.2 expression in gastric cancer tumors after treatment with saline, high, medium, and low doses of [131I]I-Zolbetuximab.

• Targeted Binding: In vitro tests showed high binding and internalization in MKN45-CLDN18.2 cells (high CLDN18.2 expression), with minimal uptake in low-expression cells, confirming specificity.
• Tumor Accumulation: In vivo, tumor uptake peaked at 3.07%ID/g 48 hours post-administration, with detectable levels after 7 days. Normal organs showed low uptake, and the tumor-to-non-tumor ratio increased over time.
• Efficacy: In MKN45-CLDN18.2 mouse models, higher doses improved tumor suppression, with the high-dose group achieving a median survival of 50 days versus less than 30 days in controls.
• Safety: No significant toxicity was observed in major organs (via H&E staining and ALT/BUN levels), with stable body weight and no adverse reactions.

How Does It Compare to Existing Gastric Cancer Treatments?

Traditional gastric cancer treatments vary in their approach, benefits, and drawbacks:

Radiolabeled antibodies like [131I]I-Zolbetuximab provide a unique edge: deep tissue penetration, no reliance on the patient’s immune system, and precise tumor targeting with minimal damage to healthy cells.

Zolbetuximab’s Journey: From Niche Target to Clinical Success

Zolbetuximab, originally IMAB362, was developed by Ganymed Pharmaceuticals in Germany over a decade ago, targeting the then-overlooked CLDN18.2 protein. In 2016, Astellas acquired Ganymed for €1.3 billion, a bold move hailed as a strategic bet on a niche target. The 2023 SPOTLIGHT Phase III trial, published in The Lancet, confirmed Zolbetuximab’s efficacy: when combined with mFOLFOX6, it extended median progression-free survival to 10.6 months in CLDN18.2-positive, HER2-negative gastric cancer patients—nearly double the control group. In 2024, Astellas submitted Zolbetuximab for regulatory approval, cementing CLDN18.2’s role in gastric cancer therapy.

abinScience: Advancing Targeted Therapy Research

abinScience supplied the research-grade Zolbetuximab for this study, providing high-quality biological reagents to support global researchers. Specializing in oncology, immunology, and neuroscience, abinScience offers a product line that includes antibodies, recombinant proteins, and detection kits, known for their high sensitivity and specificity. These tools empower innovative research in targeted therapies, advancing the development of novel treatments like those for gastric cancer.