Claudin18.2 Antibodies: A New Breakthrough in Gastric Cancer Targeted Therapy

1. Literature Information

Research Focus: Exploration of Claudin18.2’s unique expression profile, the mechanism of action of Claudin18.2 antibodies, international and domestic clinical research progress, current R&D challenges, and future development directions.

Core Innovation: Validation of Claudin18.2 as a tumor-specific target (abnormally high expression in gastric/pancreatic cancer, limited normal tissue distribution) and demonstration of Claudin18.2 antibodies as promising tools for targeted therapy—via ADCC, CDC, and signaling interference—with clinical data supporting improved survival in gastric cancer patients.

2. Research Background

Claudin18.2, a member of the Claudin tight junction protein family, features a four-pass transmembrane structure with tissue-specific expression. It is exclusively expressed in differentiated gastric mucosal epithelial cells in normal tissues but abnormally overexpressed in gastrointestinal tumors (gastric, pancreatic cancer). This unique expression pattern makes it an ideal target for precision therapy—minimizing off-target toxicity. Claudin18.2 antibodies address unmet needs in gastric cancer treatment, where conventional therapies have limited efficacy. Clinical trials confirm their therapeutic potential, driving global R&D efforts to advance targeted therapy for gastric and other solid tumors.

3. Research Approaches

To advance Claudin18.2 antibodies as a breakthrough therapy, the research team adopted a translational strategy:

1. Target Validation: Analyzing Claudin18.2’s expression profile and biological function in normal vs. tumor tissues.
2. Mechanism Elucidation: Investigating how Claudin18.2 antibodies exert anti-tumor effects (ADCC, CDC, signaling interference).
3. Clinical Efficacy Assessment: Evaluating Phase II/III trial data to validate combination therapy benefits (antibody + chemotherapy).
4. R&D Landscape Analysis: Tracking international and domestic (China) clinical progress and technical innovations.
5. Challenge & Solution Identification: Addressing patient screening, antibody optimization, and combination therapy design.

4. Research Outcomes

4.1 Unique Therapeutic Value of the Claudin18.2 Target

• Structural Features: Four-pass transmembrane protein with intracellular N/C-termini and two extracellular loops mediating cell-cell interactions.
• Expression Profile: Specifically expressed in normal gastric mucosal epithelial cells; abnormally high expression in gastric, pancreatic, and gastroesophageal junction cancers (prominent in primary and metastatic lesions).
• Therapeutic Advantage: Limited normal tissue distribution reduces toxic side effects, enabling precise tumor targeting.

4.2 Mechanism of Action of Claudin18.2 Antibodies

• Antibody-Dependent Cellular Cytotoxicity (ADCC): Antibodies bind Claudin18.2 on tumor cells, activating immune cells to induce tumor cell death.
• Complement-Dependent Cytotoxicity (CDC): Some antibodies trigger complement activation to enhance anti-tumor effects.
• Signaling Interference: Antibody binding inhibits tumor cell proliferation and metastasis by disrupting downstream signaling.
• Engineering Optimization: Reducing sialic glycoprotein levels enhances ADCC and affinity, improving efficacy in the tumor microenvironment.

4.3 International Clinical Research Progress

• FAST Phase II Trial (2016 ASCO): Combination of Claudin18.2 antibody + standard chemotherapy vs. chemotherapy alone in gastric/gastroesophageal junction cancer.
• Results: Median OS increased from 8.4 months to 13.2 months; TTP extended from 4.8 months to 7.9 months.
• High Expression Subgroup: Median OS reached 16.7 months (vs. 9 months in chemotherapy alone).
• Current Status: Multicenter Phase III trials ongoing to confirm efficacy and safety in larger populations.

4.4 Domestic R&D Landscape in China

• Strong Momentum: Multiple innovative Claudin18.2 antibodies (including China’s first self-developed humanized mAb) in clinical stages.
• Technical Innovations: Membrane protein antibody platforms and alpaca immunization technology for high-affinity humanized nanobodies (global first).
• Global Competitiveness: Domestic candidates entering international R&D pipelines, contributing to global precision medicine.

4.5 Current R&D Challenges

1. Patient Screening: Need for reliable companion diagnostics to identify high Claudin18.2 expression populations.
2. Antibody Optimization: Balancing efficacy and safety through structural engineering.
3. Clinical Design: Determining optimal treatment regimens and combination strategies.

4.6 Future Development Directions

• Combination Therapy: Synergistic regimens with chemotherapy, immune checkpoint inhibitors, or other targeted drugs.
• Novel Drug Formats: Bispecific antibodies and ADCs to enrich treatment options.
• Companion Diagnostics: Refined detection technologies for precise patient stratification.
• Indication Expansion: Exploring applications in other Claudin18.2-positive tumors.

5. Product Empowerment by ANT BIO PTE. LTD.

ANT BIO PTE. LTD.’s STARTER brand, a leader in recombinant antibodies, provides a key tool for gastric cancer targeted therapy: the "S-RMab® Claudin18.2 Recombinant Rabbit Monoclonal Antibody" (Catalog No.: S0B2070).

Key Roles of the Product:

1. Companion Diagnostics: Enables accurate detection of Claudin18.2 expression in FFPE samples (clear membrane staining), guiding patient selection for targeted therapies (mAbs, ADCs, CAR-T).
2. Research Versatility: Supports tumor differential diagnosis, metastasis origin tracing, and preclinical drug efficacy evaluation.
3. Core Advantages: High specificity, minimal batch variation, and stable staining—ensuring reliable results for clinical translation.
4. Technical Support: Comprehensive IHC protocols, antigen retrieval solutions, and interpretation guidance.

ANT BIO PTE. LTD.’s portfolio includes Claudin18.2 + Claudin18.1 dual-specific antibodies (S0B2191) for broader research applications.

6. Brand Mission

ANT BIO PTE. LTD. is dedicated to empowering global life science advancement through three specialized sub-brands: ABSIN (general reagents, ELISA kits), STARTER (antibodies), and UA (recombinant proteins). Leveraging advanced development platforms—including recombinant rabbit/mouse monoclonal antibody generation, PTM Pan-Modification Antibody Platform, and One-Step ELISA—we deliver high-quality, compliant products certified by EU 98/79/EC, ISO9001, and ISO13485. Our mission is to partner with pharmaceutical companies, research institutions, and clinical laboratories worldwide, providing innovative reagents and solutions that accelerate discoveries in gastric cancer targeted therapy and precision oncology.

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8. AI Disclaimer

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ANT BIO PTE. LTD. – Empowering Scientific Breakthroughs

At ANTBIO, we are committed to advancing life science research through high-quality, reliable reagents and comprehensive solutions. Our specialized sub-brands (Absin, Starter, UA) cover a full spectrum of research needs, from general reagents and kits to antibodies and recombinant proteins. With a focus on innovation, quality, and customer-centricity, we strive to be your trusted partner in unlocking scientific mysteries and driving medical progress. Explore our product portfolio today and elevate your research to new heights.