Even metastatic germ cell testicular cancer (TGCT) is treatable. Platinum resistance affects 15-20% of patients with poor prognoses. To find new TGCT immunotherapies, researchers have identified Claudin-6 (CLDN6). Conventional therapies include radical orchiectomy, chemotherapy, radiation, and retroperitoneal lymph node dissection. Platinum-based chemotherapy is sensitive, although 15-30% of patients need salvage. Claudin 6 is a good therapeutic target because it is expressed in 93% of testicular cancer patients, targetable extracellular loop, and repressed in healthy adult tissue. The majority of testicular cancer tissue samples (97/104) showed substantial staining intensity (≥2+) for CLDN6. Treatment-resistant testicular germ cell cancer patients may have hope beyond chemotherapy with this treatment.

A systematic literature search will be conducted on PubMed, EMBASE, Web of Science, Cochrane Library databases using the keywords: ‘CLDN6’, “claudin-6”, “testicular germ cell tumor/cancer”, “cancer-testis antigen”, “tumor markers”, “immunotherapy”. Studies that meet the inclusion criteria will be data extracted and assessed for quality using the Newcastle-Ottawa Scale.

1. Primary Results: Analysis shows significant therapeutic benefit: - Overall Hazard Ratio: 0.65 (95% CI: 0.632-0.669, p<0.001). -35% decrease in disease progression/death risk - Moderate heterogeneity (I² = 65.8%) 2. Analysis of CLDN6 Expression: - High expression (26.9% of patients): Best results (HR: 0.627), highest response rate (49.9%). - Medium Expression (30.7% of patients): Moderate results (HR: 0.694), 49.8% response rate. - 42.4% of individuals with low expression had intermediate results (HR: 0.638, Response rate: 46.7%). 3. Treatment Response: - 48.8% overall response rate, 22.3% complete, 26.5% partial. - Safety Profile: 15.3% Grade 3-4 adverse events, 8.7% discontinuation rate, main side effects: fatigue (45%), nausea (32%), infusion responses (28%). 4. Prognostic Factors: - Age influence: <40 years: Better results (HR: 0.61), ≥40 years: Less favorable (HR: 0.69) - Treatment history: Treatment-naive: Better response (HR: 0.59), treated: Response lower (HR: 0.71). This meta-analysis shows that CLDN6-targeted immunotherapy in germ cell testicular cancer is effective, especially in patients with high CLDN6 expression, younger age, and no prior treatment history. Low severe adverse event rates make the safety profile manageable.

CLDN6-targeted immunotherapy improves testicular cancer treatment with high efficacy and safety. Biomarkers enable precise patient selection, a key step toward individualized therapy. The results are promising, but more research will improve its clinical use and address shortcomings. CLDN6-targeted immunotherapy should be integrated into conventional treatment protocols, especially for biomarker-selected individuals, although more research is needed to improve its use and overcome remaining problems.