Pancreatic cancer remains one of the deadliest and most difficult-to-treat cancers worldwide. Often diagnosed at an advanced stage and resistant to many conventional therapies, it continues to present major challenges for patients, families, and healthcare professionals alike.
In recent years, a promising new target known as CLDN18.2 has attracted growing attention in the field of precision oncology. Researchers believe this target could open the door to more effective and personalized treatment strategies for pancreatic cancer.
What is CLDN18.2?
CLDN18.2 is a protein that belongs to the claudin family, which plays an important role in the tight junctions that connect cells together. In healthy tissues, CLDN18.2 is primarily found in the stomach lining and is largely hidden within these cellular junctions, making it inaccessible to the immune system and most therapies.
However, when cells become cancerous, these tight junctions can break down, exposing CLDN18.2 on the surface of tumor cells. This makes it an attractive therapeutic target because it is highly expressed on cancer cells while remaining largely absent from normal tissues.
Researchers have identified CLDN18.2 expression in several gastrointestinal cancers, including gastric cancer and pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer.
Why does CLDN18.2 matter in pancreatic cancer?
Studies suggest that approximately 50% to 60% of pancreatic ductal adenocarcinomas express CLDN18.2. Importantly, normal pancreatic tissue shows little to no expression of the protein, making it a highly tumor-specific target.
Some research has also indicated that patients with CLDN18.2-positive pancreatic cancer may experience slightly improved survival outcomes compared with those whose tumors do not express the target. More importantly, the presence of CLDN18.2 creates an opportunity for targeted therapies that can selectively attack cancer cells while minimizing damage to healthy tissue.
Emerging CLDN18.2-targeted therapies
Researchers are currently pursuing multiple therapeutic approaches aimed at CLDN18.2.
Monoclonal antibodies
Monoclonal antibodies were among the first CLDN18.2-targeted therapies to enter clinical development.
The most well-known example is zolbetuximab, which received approval in Japan in 2024 for the treatment of certain patients with gastric cancer. While the drug demonstrated the potential of CLDN18.2-targeted treatment, studies in pancreatic cancer have produced mixed results. The Phase II GLEAM trial, for example, did not meet its primary overall survival endpoint, highlighting the challenges of treating pancreatic cancer.
Bispecific antibodies
Bispecific antibodies are designed to bind both CLDN18.2 on tumor cells and immune cells such as T cells, effectively bringing the immune system directly to the cancer.
One of the most advanced candidates is QLS31905, a CLDN18.2/CD3 bispecific antibody developed by Qilu Pharmaceutical. According to data presented at the 2026 ASCO Annual Meeting, QLS31905 combined with chemotherapy achieved an objective response rate of 59.8% and a disease control rate of 89.0% in patients with CLDN18.2-positive advanced pancreatic cancer. Encouraging activity was also observed in patients with low CLDN18.2 expression.
Another promising agent is spevatamig (PT886), which targets both CLDN18.2 and CD47. Early clinical results presented at the 2026 ASCO Gastrointestinal Cancers Symposium showed a disease control rate of 93% and an objective response rate of 40% when combined with chemotherapy in metastatic pancreatic cancer. The therapy has received both Orphan Drug and Fast Track designations from the U.S. FDA.
Antibody-drug conjugates (ADCs)
ADCs combine the targeting precision of antibodies with the cancer-killing power of highly potent drugs.
Several CLDN18.2-targeted ADCs are currently being evaluated in clinical trials. Among them, IBI343 developed by Innovent Biologics has received Breakthrough Therapy designation in China for previously treated CLDN18.2-positive advanced pancreatic cancer.
Additional candidates such as BA1301 and BL-M05D1 have also demonstrated encouraging early-stage clinical activity, supporting continued development of this therapeutic class.
CAR-T cell therapy
CAR-T cell therapy represents one of the most innovative approaches in cancer treatment. The therapy involves collecting a patient’s T cells, genetically engineering them to recognize specific cancer targets, and then infusing them back into the patient.
Satri-cel, a CLDN18.2-targeted CAR-T therapy developed by CARsgen Therapeutics, has generated considerable interest. Data presented at the 2025 ESMO Congress showed encouraging outcomes in a small group of high-risk pancreatic cancer patients who received Satri-cel following curative surgery. Most patients remained disease-free during follow-up, and significant reductions in the tumor marker CA19-9 were observed.
Researchers are also exploring dual-target CAR-T therapies that simultaneously target CLDN18.2 and mesothelin (MSLN) to overcome tumor heterogeneity and treatment resistance.
Challenges remain
Despite the excitement surrounding CLDN18.2-targeted therapies, significant challenges remain.
Pancreatic cancer is often described as an “immune desert” because its tumor microenvironment suppresses immune activity and limits the effectiveness of immunotherapy. Overcoming this barrier remains a major focus of ongoing research.
Scientists are also investigating mechanisms of resistance. Recent studies suggest that KRAS-driven molecular pathways may reduce sensitivity to CLDN18.2-targeted treatments. Encouragingly, early research indicates that combining CLDN18.2-targeted therapies with KRAS inhibitors could enhance treatment effectiveness.
In addition, radiation therapy may improve the performance of CLDN18.2-targeted CAR-T cells by making tumors more susceptible to immune attack.
Looking ahead
The future of CLDN18.2-targeted therapy in pancreatic cancer is likely to involve more precise patient selection, innovative drug combinations, and earlier use of these therapies in the treatment journey.
As bispecific antibodies, ADCs, and CAR-T therapies continue to advance through clinical development, CLDN18.2 is emerging as one of the most important targets in pancreatic cancer research.
While most of these treatments remain investigational, they represent a rapidly evolving area that could significantly expand treatment options for patients facing one of the world’s most challenging cancers.
