SHR-A1904

In 2024, the field of cancer therapeutics has witnessed remarkable progress in targeting Claudin 18.2 (CLDN18.2). As a protein highly expressed in several malignancies—particularly gastrointestinal cancers such as gastric and pancreatic cancer—CLDN18.2 has emerged as a highly promising therapeutic target. Antibody-drug conjugates (ADCs) developed against this target, including Zolbetuximab, IBI-343, LM-302, and SHR-A1904, have shown encouraging preclinical and clinical results. These innovations not only improve patient survival but also pave the way for more personalized treatment approaches. By selectively recognizing and attacking tumor cells while minimizing damage to normal tissues, these agents are redefining the landscape of cancer therapy. CLDN18.2 is an isoform of Claudin-18, which belongs to the Claudin family of proteins. This family comprises transmembrane proteins that play crucial roles in maintaining tight junctions between epithelial and endothelial cells. Tight junctions function as both physical barriers, preventing the free passage of substances through the paracellular space, and as regulators of ion and small molecule permeability. The depiction of Claudin protein structures1 Structurally, Claudins share common features, including four transmembrane domains, two extracellular loops (ECL1 and ECL2), and intracellular N- and C-termini. CLDN18.2 is predominantly expressed in differentiated epithelial cells of the gastric mucosa, exhibiting highly specific expression under normal physiological conditions. However, during malignant transformation, the disruption of tight junctions caused by uncontrolled tumor proliferation can expose CLDN18.2 epitopes, making them accessible for targeted therapeutic intervention. Main characteristics of claudins2 From a proliferation perspective, evidence suggests that CLDN18.2 may interfere with intercellular communication and signal transduction pathways, influencing the cell cycle and promoting tumor growth. High expression of CLDN18.2 has been associated with increased tumor cell proliferation in several studies, likely due to its role in maintaining cell polarity and regulating cell growth. In terms of invasion and metastasis, abnormal activation of the CLDN18.2 gene may alter cell membrane functionality and enhance tissue permeability. This disruption facilitates tumor cells in breaching the basement membrane and invading surrounding tissues, thus promoting both local and distant metastases. Aberrant CLDN18.2 expression also impairs normal cell polarity and structural integrity, further weakening tissue barriers and enabling cancer cell dissemination. While CLDN18.2 expression is typically confined to gastric mucosal cells under normal conditions, it is significantly upregulated in various cancers, including gastric and pancreatic cancers. This persistent expression even after malignant transformation, combined with exposure of the epitope due to tight junction disruption, makes CLDN18.2 an attractive target for antibody-based therapies, particularly in cancers with limited treatment options. ADC Therapies Targeting CLDN18.2Zolbetuximab: The First Approved CLDN18.2-Targeted Monoclonal AntibodyZolbetuximab is the first globally approved therapeutic specifically targeting CLDN18.2. It is a chimeric IgG1 monoclonal antibody designed for the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinomas. By binding selectively to CLDN18.2, a transmembrane protein highly expressed on certain gastric cancer cells, Zolbetuximab induces direct cancer cell death. Moreover, it activates two major immune-mediated mechanisms: antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). ADCC involves the recruitment of immune effector cells, such as natural killer (NK) cells, to the tumor site, leading to targeted destruction of cancer cells.CDC triggers the complement system to form membrane attack complexes (MACs) that lyse tumor cells.The development of Zolbetuximab was underpinned by its successful performance in two pivotal Phase III clinical trials—SPOTLIGHT and GLOW. In the SPOTLIGHT trial, Zolbetuximab combined with mFOLFOX6 chemotherapy significantly improved progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone: Median PFS: 10.61 months vs. 8.67 monthsMedian OS: 18.23 months vs. 15.54 monthsSimilarly, the GLOW trial demonstrated that Zolbetuximab combined with CAPOX chemotherapy also yielded superior outcomes compared to CAPOX alone. Based on these positive results, Zolbetuximab has received regulatory approval in multiple countries and regions, including Japan, the United States, and the European Union, for the treatment of specific subtypes of gastric cancer. It remains the first and only approved CLDN18.2-targeted therapy to date. Although initially developed for gastric and GEJ adenocarcinomas, Zolbetuximab’s therapeutic potential could extend to other malignancies, such as pancreatic, biliary tract, esophageal, and lung cancers, where CLDN18.2 expression is also elevated. Expression testing is typically required to identify patients who are most likely to benefit from Zolbetuximab therapy. As understanding of CLDN18.2 biology deepens, it is anticipated that Zolbetuximab could be explored in combination strategies, such as with immune checkpoint inhibitors or other targeted therapies, to further enhance efficacy and reduce adverse effects. Additionally, the success of Zolbetuximab has catalyzed the development of next-generation CLDN18.2-targeted agents, promising new hope for patients with limited treatment options. These advances are expected to significantly contribute to the evolution of personalized cancer care, enabling more precise, effective, and individualized therapeutic strategies. Bispecific Antibody LB-4330LB-4330 is a bispecific antibody developed by L&L Biopharma, designed to leverage its dual-targeting capability to activate CD8+ T cells within the tumor microenvironment, thereby enhancing the body's immune response against cancer. By doing so, LB-4330 not only directly attacks cancer cells but also mobilizes the patient’s immune system for a more effective and sustained anti-tumor response. The mechanism of action of LB-4330 relies on its unique structural design, which enables simultaneous binding to CLDN18.2 and specific receptors on the surface of CD8+ T cells. This dual specificity allows LB-4330 to accumulate at tumor sites and activate T cells, triggering the release of cytotoxic substances to kill cancer cells. Moreover, LB-4330 may also enhance anti-tumor immunity through additional, less well-characterized mechanisms, such as modifying the tumor microenvironment or improving dendritic cell function. These features position LB-4330 as a promising therapeutic candidate, particularly for patients with advanced or metastatic cancers that are resistant to conventional treatments. The major CD8+ T cell states in human tumors3 Currently, LB-4330 is in Phase II clinical development, focusing on evaluating its safety and efficacy in patients with advanced or metastatic solid tumors. According to information released by L&L Biopharma, LB-4330 has shown encouraging potential in an open-label, Phase Ib/II dose-escalation and expansion study. This study aims to explore the drug’s effects at various doses to identify an optimal dosing range that maximizes therapeutic benefit while minimizing adverse events. Although detailed clinical results have yet to be fully disclosed, preliminary data indicate that LB-4330 is well-tolerated and has demonstrated meaningful clinical activity in certain patient populations. Beyond its established indications in gastric cancer, pancreatic cancer, and ovarian cancer, researchers are investigating the potential of LB-4330 in other tumor types. Given the widespread expression of CLDN18.2 across multiple malignancies, LB-4330 could emerge as a broad-spectrum anti-cancer agent. Furthermore, as understanding of CLDN18.2 biology deepens and combination strategies with other therapies (such as chemotherapy, radiotherapy, or immunotherapy) are explored, the application prospects for LB-4330 appear increasingly expansive. Despite its promising profile, several challenges must be addressed before LB-4330 can be widely adopted. These include the need to accurately identify patients most likely to benefit from the therapy—often requiring precise measurement of CLDN18.2 expression—and the necessity for long-term safety evaluations. Additionally, further mechanistic studies, optimization of dosing strategies, and identification of ideal combination regimens with existing therapies will be critical to fully unlocking LB-4330’s therapeutic potential. CLDN18.2-Targeting ADCsSeveral antibody-drug conjugates (ADCs) have been developed to target Claudin 18.2 (CLDN18.2), including IBI-343, LM-302, SHR-A1904, ATG-022, Sonestatug vedotin, and SKB-315. These agents utilize a specific antibody to recognize and bind to CLDN18.2 antigens on the surface of cancer cells, delivering a potent cytotoxic payload intracellularly to induce tumor cell death. Developed by companies such as Innovent Biologics, LaNova Medicines, Hengrui Medicine, Antengene Corporation, and Kelun-Biotech, these ADCs span various stages of clinical development (from Phase II to Phase III) and show promise in treating gastric cancer, esophageal cancer, and other CLDN18.2-positive solid tumors. 1) IBI-343IBI-343 is an innovative ADC developed by Innovent Biologics. It combines a highly specific anti-CLDN18.2 antibody with a cytotoxic small-molecule drug. This design enables precise targeting of CLDN18.2-expressing tumor cells, facilitating selective delivery of the cytotoxic agent and minimizing damage to normal tissues, thus improving both safety and efficacy. In preclinical studies, a single administration of IBI-343 significantly inhibited tumor growth in xenograft models with low antigen expression, maintaining low tumor volumes for up to 21 days. This finding suggests that IBI-343 is not only effective against tumors with high CLDN18.2 expression but also shows robust activity in tumors with lower antigen levels. This bystander effect enhances IBI-343’s appeal as a cancer therapeutic, particularly in tumors with heterogeneous antigen expression within the tumor microenvironment. IBI-343 has been granted Breakthrough Therapy Designation by China’s National Medical Products Administration (NMPA) for two indications: (1) advanced gastric/gastroesophageal junction adenocarcinoma patients with positive CLDN18.2 expression who have received at least two prior systemic therapies, and (2) advanced pancreatic ductal adenocarcinoma patients with positive CLDN18.2 expression who have received at least one prior systemic therapy. This designation accelerates the development timeline and underscores the potential importance of IBI-343 as a novel treatment option, particularly for patients with difficult-to-treat cancers. 2) LM-302LM-302 is an antibody-drug conjugate (ADC) developed by Lanpu Biopharmaceuticals (also known as Lansion Biotechnology). This investigational therapy combines a highly specific anti-CLDN18.2 monoclonal antibody with a cytotoxic payload, monomethyl auristatin E (MMAE). The design enables the antibody to selectively bind to the CLDN18.2 antigen expressed on tumor cell surfaces and deliver the cytotoxic agent directly into cancer cells, thereby achieving targeted tumor cell killing. As of the latest updates, LM-302 has been granted three Orphan Drug Designations (ODDs) by the U.S. Food and Drug Administration (FDA) for the treatment of pancreatic cancer, gastric cancer, and gastroesophageal junction (GEJ) cancer. In China, LM-302 has advanced into Phase III clinical trials, indicating that the drug has demonstrated sufficient safety and preliminary efficacy in earlier studies and is now undergoing larger, more diverse patient evaluations to confirm its therapeutic potential. Moreover, LM-302 has been proposed for inclusion under China’s National Medical Products Administration (NMPA)/Center for Drug Evaluation (CDE) Breakthrough Therapy designation. The targeted indication is for patients with locally advanced or metastatic gastric or GEJ adenocarcinoma who are CLDN18.2-positive and have received at least two prior lines of systemic therapy. A Phase II clinical trial is also underway to evaluate the efficacy, safety, and tolerability of LM-302 in combination with toripalimab (an anti-PD-1 antibody) in patients with CLDN18.2-positive advanced gastrointestinal tumors. The primary endpoint of this study is to assess the efficacy of the LM-302 and toripalimab combination, with secondary objectives including safety, pharmacokinetics, immunogenicity, and the correlation between CLDN18.2/PD-L1 expression and antitumor activity. It is worth noting that Lanpu Biopharmaceuticals had previously entered into an exclusive licensing agreement with Turning Point Therapeutics, granting Turning Point rights to develop and commercialize LM-302 outside of Greater China and South Korea. However, following Bristol Myers Squibb’s acquisition of Turning Point, the licensing status of LM-302 has shifted, and the asset is now listed as "global" in ownership. 3) SHR-A1904SHR-A1904 is an ADC independently developed by Hengrui Medicine. It consists of a highly specific anti-CLDN18.2 antibody linked to a cytotoxic payload—a topoisomerase inhibitor (TOPOi). This design enables the ADC to selectively bind to CLDN18.2-expressing tumor cells and deliver its potent payload intracellularly, resulting in targeted cancer cell death. At the 2024 European Society for Medical Oncology (ESMO) Congress, early clinical data on SHR-A1904 were presented for the treatment of patients with CLDN18.2-positive gastric cancer and gastroesophageal junction adenocarcinoma (GC/GEJC). The results demonstrated manageable safety and promising antitumor activity, with an objective response rate (ORR) of 55.6% and a disease control rate (DCR) of 88.9%. Beyond gastric cancer, SHR-A1904 is also being investigated for other CLDN18.2-expressing solid tumors, highlighting its broad therapeutic potential. Notably, Hengrui Medicine entered into a collaboration agreement with Merck KGaA, Darmstadt, Germany, valued at up to €1.4 billion. Under this agreement, Merck has secured global exclusive development, manufacturing, and commercialization rights for SHR-A1904 outside of mainland China. This strategic partnership reflects strong international recognition of SHR-A1904's potential and positions it for global success. SHR-A1904 has been evaluated across multiple dose levels. The 6.0 mg/kg cohort demonstrated the best efficacy, achieving an ORR of 55.6% and a DCR of 88.9%. The safety profile was considered manageable, although some dose-limiting toxicities (DLTs) were observed at higher doses. With ongoing Phase III clinical trials, SHR-A1904 is poised to become a promising new treatment option for patients with CLDN18.2-positive cancers. Furthermore, through its international collaborations, SHR-A1904 is expected to benefit a broader patient population worldwide. ConclusionAs a member of the Claudin family, Claudin 18.2 (CLDN18.2) plays a vital role in maintaining tight junctions between epithelial and endothelial cells and is aberrantly overexpressed in various cancer types. This unique biological characteristic makes CLDN18.2 an ideal target for cancer therapy. Several CLDN18.2-targeted antibody-drug conjugates (ADCs)—including Zolbetuximab, IBI-343, LM-302, and SHR-A1904—have demonstrated significant antitumor activity with favorable safety profiles. Particularly, Zolbetuximab has achieved groundbreaking clinical success as the first approved therapy targeting CLDN18.2 for the treatment of gastric and gastroesophageal junction adenocarcinoma. Additionally, bispecific antibodies such as LB-4330, which enhance antitumor immune responses, are further expanding the therapeutic landscape of CLDN18.2 targeting. Globally, research on CLDN18.2-targeted therapies has become a major area of focus. More than 90 candidate therapies targeting CLDN18.2—including monoclonal antibodies, bispecific antibodies, CAR-T cells, and ADCs—are currently under development. The success of programs such as IBI-343 not only highlights the innovation capacity of Chinese biopharmaceutical companies but also provides valuable models for future drug development. As clinical trials progress and technologies advance, CLDN18.2-targeted therapies are expected to offer new hope for a broader range of cancer patients, driving forward the era of personalized medicine and precision oncology. These developments mark a deeper understanding of cancer biology and herald the arrival of more CLDN18.2-based therapies, ultimately benefiting patients worldwide. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery! Reference 1. Cao W, Xing H, Li Y, Tian W, Song Y, Jiang Z, Yu J. Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy. Biomark Res. 2022 May 31;10(1):38. doi: 10.1186/s40364-022-00385-1. PMID: 35642043; PMCID: PMC9153115.2. Kubota Y, Shitara K. Zolbetuximab for Claudin18.2-positive gastric or gastroesophageal junction cancer. Ther Adv Med Oncol. 2024 Jan 3;16:17588359231217967. doi: 10.1177/17588359231217967. PMID: 38188462; PMCID: PMC10768589.3. van der Leun AM, Thommen DS, Schumacher TN. CD8+ T cell states in human cancer: insights from single-cell analysis. Nat Rev Cancer. 2020 Apr;20(4):218-232. doi: 10.1038/s41568-019-0235-4. Epub 2020 Feb 5. PMID: 32024970; PMCID: PMC7115982.

In the forefront of oncology, scientists have been tirelessly searching for new weapons capable of precisely targeting cancer cells without harming healthy tissues. In recent years, a molecular target known as Claudin18.2 has emerged as a prominent target in the treatment of gastric cancer, pancreatic cancer, and various other solid tumors. As a member of the tight junction protein family, Claudin18.2 is normally expressed exclusively in differentiated gastric mucosal epithelial cells, while exhibiting highly specific overexpression in several cancers, including gastric and pancreatic cancers. This unique expression pattern makes Claudin18.2 an ideal target for anticancer drug development. Global Transactions of Claudin18.2 Targeting Drugs in Patsnap SynapseMechanism of Action for Targeting Claudin18.2Claudin18.2 is a member of the Claudin protein family, which constitutes an essential component of tight junctions (TJs). The Claudin family comprises at least 27 members whose primary function is to form barriers between cells, maintaining tissue polarity and selective permeability. Claudin18.2 is encoded by the CLDN18 gene and features four transmembrane domains (TM1–4), intracellular N-terminal and C-terminal ends, and two extracellular loops (ECL1 and ECL2). ECL1 contains four β-strands and an extracellular helix (ECH), while ECL2 includes one β-strand and a partially membrane-exposed extracellular segment. These structural features enable Claudin18.2 to form selective permeability barriers between cells, supporting the polarity of gastric epithelial cells. Claudin 18.2 structure, function and expression patterns2Under normal conditions, Claudin18.2 is expressed at low levels in the differentiated epithelial cells of the gastric mucosa, where it primarily functions to facilitate intercellular connections and maintain barrier integrity. However, during the malignant transformation of gastric mucosal epithelial tissues, disruptions in cell polarity expose the Claudin18.2 epitopes on the cell surface, making it a potential therapeutic target. Claudin 18.2 expression during malignant transformation2As a critical component of intercellular tight junctions, Claudin18.2 primarily functions to preserve intercellular barrier integrity. However, in specific cancer types—particularly gastric cancer—the expression profile of Claudin18.2 differs significantly from that in normal tissues. During the malignant transformation of gastric mucosal epithelial tissues, the loss of cell polarity exposes the Claudin18.2 epitopes on the cell surface. This phenomenon not only positions Claudin18.2 as a promising therapeutic target for gastric cancer but also provides new perspectives for developing targeted therapeutic strategies. The Role of Claudin18.2 in TumorsThe aberrant expression of Claudin18.2 is closely associated with the progression of various cancers. In normal tissues, Claudin18.2 is primarily restricted to differentiated epithelial cells in the gastric mucosa. However, in tumor tissues, the expression level of this protein is significantly elevated. More importantly, the epitopes of Claudin18.2 on the surface of tumor cells become readily accessible to antibodies under pathological conditions, enabling the potential for specific targeted therapies. The high expression of Claudin18.2 can enhance tumor cell adhesion and communication with surrounding cells, influencing cellular growth, proliferation, and metastasis. For instance, the overexpression of Claudin18.2 may promote tumor cell proliferation through the activation of signaling pathways such as PI3K/Akt and MAPK. Mechanisms of action of the various classes of developmental claudin 18.2-targeted therapies2Zolbetuximab is a monoclonal antibody targeting Claudin18.2 that specifically binds to the Claudin18.2 protein on the surface of tumor cells. Claudin18.2 is highly expressed in various cancers, especially gastric cancer, pancreatic cancer, and lung cancer. Zolbetuximab exerts its therapeutic effect primarily by inducing antibody-dependent cellular cytotoxicity (ADCC), activating natural killer (NK) cells and other immune cells, such as macrophages and neutrophils. These immune cells directly kill antibody-bound tumor cells by releasing cytotoxic granules (e.g., perforin and granzymes) or expressing death ligands (e.g., FasL). Additionally, Zolbetuximab enhances the killing of tumor cells through complement-dependent cytotoxicity (CDC) and apoptosis-inducing mechanisms. Mechanism of action of claudiximab3When combined with certain immunomodulatory agents (e.g., zoledronic acid and interleukin-2), Zolbetuximab can activate and expand immune cell populations associated with ADCC, such as γδ T cells and NK cells, thereby augmenting the immune response against tumors. Furthermore, when used in combination with chemotherapy agents, Zolbetuximab promotes T-cell infiltration and induces the production of pro-inflammatory cytokines, leading to enhanced therapeutic efficacy. As an ideal tumor-specific target, Claudin18.2 enables the development of precision therapies that selectively attack tumor cells while minimizing damage to normal tissues, thereby improving the safety and efficacy of cancer treatment. Clinical Trial Results on the Antitumor Activity of ZolbetuximabIn two pivotal Phase III clinical trials, SPOTLIGHT and GLOW, Vyloy (zolbetuximab) combined with chemotherapy significantly improved patient survival rates. Specifically, in the SPOTLIGHT trial, the median progression-free survival (PFS) for the Vyloy combined with mFOLFOX6 chemotherapy group was 10.61 months, compared to 8.67 months for the placebo group (p<0.0001). In terms of median overall survival (OS), the Vyloy group reached 18.23 months, significantly surpassing the placebo group's 15.54 months (p=0.0013). In the GLOW trial, the median PFS for the Vyloy combined with CAPOX chemotherapy group was 8.21 months, while the placebo group's was 6.80 months (p=0.0002). The median OS was 14.39 months, markedly better than the placebo group's 12.16 months (p=0.0133). These data indicate that Vyloy can significantly delay disease progression and extend patient survival. In both the SPOTLIGHT and GLOW trials, the safety profile of Vyloy combined with chemotherapy was consistent with the known safety profiles of mFOLFOX6 and CAPOX regimens, with no new safety concerns observed. This provides a strong foundation for the widespread clinical application of Vyloy. Patients receiving Vyloy treatment can maintain a high quality of life while attaining significant therapeutic benefits. This is particularly important for patients with advanced gastric cancer, who often need to consider the impact of treatment on their quality of life. The SPOTLIGHT and GLOW trials encompassed patients from different regions and backgrounds, indicating the universality of Vyloy's therapeutic effects, making it suitable for a variety of HER2-negative, CLDN18.2-positive gastric cancer patients. This broad applicability positions Vyloy as a promising treatment option that can benefit a wider range of gastric cancer patients. Whether in Asia, Europe, or North America, Vyloy has shown significant therapeutic effects, laying the groundwork for its global promotion and application. Research and Development Landscape of Claudin18.2Claudin18.2, a target highly expressed in various tumors, has garnered the attention of multiple global pharmaceutical companies and research institutions. Currently, there are 92 drug candidates targeting Claudin18.2 in development, encompassing monoclonal antibodies, bispecific antibodies, antibody-drug conjugates (ADC), and CAR-T cell therapies, with development stages ranging from preclinical to Phase III clinical trials. This highlights the enormous potential of this target in the field of cancer therapy. Clinical Research Focus of Claudin18.2 in Patsnap SynapseThe United States and Europe have maintained significant activity in the research and development of Claudin18.2 targets. The United States has 9 drugs in development, accounting for 10.46% of the global total, primarily concentrated in the fields of monoclonal antibodies and bispecific antibodies. Europe's research and development efforts are relatively less, accounting for approximately 5% of the global total, mainly centered in Germany and the United Kingdom. Other countries such as Japan and South Korea are also conducting related research, but in smaller numbers, mostly in preclinical or early clinical stages. Overall, the Claudin18.2 target is receiving wide attention globally, with China leading the efforts, followed by the United States and Europe. China is at the forefront in the research and development of the Claudin18.2 target, with a total of 70 drugs under development, accounting for 81.4% of the global total. Major companies such as Innovent Biologics, Akeso, RemeGen, and CARsgen Therapeutics have made significant progress in the fields of monoclonal antibodies, bispecific antibodies, ADCs, and CAR-T cell therapies. Some of these drugs have entered clinical trial stages and have shown good safety and preliminary efficacy. Anti-Cancer Drugs Targeting Claudin18.2Given the unique expression of Claudin18.2 in tumor cells, multiple targeted therapy strategies are being actively researched and developed, in addition to Zolbetuximab. These strategies include but are not limited to monoclonal antibodies, bispecific antibodies, CAR-T cell therapies, and ADCs. 1. antibody-drug conjugate (ADC) SHR-A1904  SHR-A1904 is an ADC independently developed by Hengrui Pharmaceuticals, with a payload of a topoisomerase inhibitor (TOPOi). Its mechanism of action includes: specific binding, where SHR-A1904 specifically binds to antigens on the surface of CLDN18.2 positive tumor cells through its monoclonal antibody component; endocytosis and release, where the bound ADC is internalized by tumor cells, degraded by lysosomes, and releases small molecule toxins; cytotoxic effect, where the released small molecule toxins interfere with DNA replication and repair, leading to tumor cell apoptosis. This design not only enhances the drug's selective cytotoxicity towards tumor cells but also reduces toxicity to normal cells. 2.Bispecific Antibodies (BsAbs) AMG 910  AMG 910 is a bispecific antibody co-developed by Amgen and BeiGene, capable of binding simultaneously to CLDN18.2 and the CD3 molecule on the surface of T cells. Its primary mechanisms include: T cell recruitment, where AMG 910 binds to CLDN18.2 and CD3, recruiting T cells to the vicinity of tumor cells and enhancing T cell-mediated cytotoxicity; immune activation, where the binding of AMG 910 activates T cells, promoting cytokine secretion and further enhancing tumor cell killing capacity. The design of this bispecific antibody aims to improve the specificity and efficiency of immunotherapy, providing a new therapeutic approach for CLDN18.2 positive gastric cancer and other related cancers. 3.Chimeric Antigen Receptor T-cells (CAR-T) CT-041  CT-041 is a CAR-T cell therapy developed by CARsgen Therapeutics, specifically targeting CLDN18.2 positive tumor cells. Its mechanisms include: T cell modification, which involves genetically engineering T cells to express a CAR that specifically recognizes CLDN18.2; tumor cell killing, where the modified CAR-T cells specifically recognize and bind to CLDN18.2 positive tumor cells, directly killing them by releasing cytotoxic granules; immune memory, where CAR-T cells form long-term immune memory in the body, continuously monitoring and destroying recurrent tumor cells. This CAR-T cell therapy provides a new treatment option for patients with CLDN18.2 positive gastric cancer, pancreatic cancer, and other solid tumors, demonstrating good clinical efficacy and safety. Summary Despite the enormous potential of targeted therapy against Claudin18.2, several challenges remain. Firstly, accurately identifying patients who might benefit from targeted therapy is an unresolved issue. Different studies use varied detection methods and positive criteria, which may lead to difficulties in determining positive results in clinical practice. Secondly, overcoming tumor resistance and improving treatment efficacy is another focal point for future research. In conclusion, the specific expression of the Claudin18.2 protein in gastric and various other tumors provides a solid theoretical foundation for its use as a therapeutic target. With the continuous advancement of related research and technology, targeted therapy against Claudin18.2 is expected to bring benefits to more patients and open a new chapter in precise oncology treatment. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery! Refrence:  1.Mullard A. FDA approves first claudin-18.2-targeted antibody for gastric cancer. Nat Rev Drug Discov. 2024 Oct 22. doi: 10.1038/d41573-024-00172-7. Epub ahead of print. PMID: 39438629.2.Nakayama I, Qi C, Chen Y, Nakamura Y, Shen L, Shitara K. Claudin 18.2 as a novel therapeutic target. Nat Rev Clin Oncol. 2024 May;21(5):354-369. doi: 10.1038/s41571-024-00874-2. Epub 2024 Mar 19. PMID: 38503878.3.Singh P, Toom S, Huang Y. Anti-claudin 18.2 antibody as new targeted therapy for advanced gastric cancer. J Hematol Oncol. 2017 May 12;10(1):105. doi: 10.1186/s13045-017-0473-4. PMID: 28494772; PMCID: PMC5427576.