Dual-target PSMA/PSCA CAR-NK Cells in Advanced Prostate Cancer

Inclusion criteria

• Male participant age 18 years or older.
• Histologically or cytologically confirmed prostate adenocarcinoma with metastatic castration-resistant disease.
• Disease progression by PCWG3 while maintaining castrate testosterone (\<50 ng/dL) with ongoing androgen deprivation therapy or prior orchiectomy.
• Documented PSMA and/or PSCA expression by a validated tumor assay; PSMA PET may support target confirmation when applicable.
• Prior progression on at least one androgen receptor pathway inhibitor such as abiraterone, enzalutamide, apalutamide, or darolutamide; prior taxane, PARP inhibitor, radioligand therapy, or checkpoint inhibitor is allowed.
• ECOG performance status 0 or 1.
• Adequate hematologic, renal, hepatic, cardiac, and pulmonary function per protocol laboratory thresholds.
• At least one measurable lesion by RECIST 1.1 or evaluable bone-predominant disease by PCWG3.
• Life expectancy of at least 12 weeks.
• Ability to understand and sign informed consent and willingness to provide required blood and tissue samples.

Exclusion criteria

• Active central nervous system metastases or leptomeningeal disease.
• Dominant small-cell or neuroendocrine prostate cancer histology.
• Prior gene-modified cellular therapy within 6 months before lymphodepletion, or prior allogeneic transplant requiring ongoing systemic immunosuppression.
• Active autoimmune disease requiring systemic treatment or chronic immunosuppression; systemic corticosteroid use greater than 10 mg prednisone equivalent daily within 7 days of lymphodepletion.
• Uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, or HIV infection.
• Clinically significant cardiovascular disease, symptomatic arrhythmia, recent myocardial infarction, or uncontrolled heart failure.
• Unresolved grade 2 or higher toxicity from prior anticancer therapy, except alopecia, stable endocrinopathy, or other protocol-approved exceptions.
• Another active malignancy requiring systemic treatment.
• Any medical, psychiatric, or laboratory abnormality that, in the investigator's judgment, would increase risk or interfere with study interpretation.