Dual-Target CSPG4/GD2 CAR-NK Cells for Advanced Melanoma

Inclusion Criteria:

* Age 18-75 years at consent.
* Histologically confirmed unresectable/metastatic cutaneous melanoma or metastatic uveal melanoma.
* Disease progression after standard therapy, intolerance to standard therapy, or no remaining standard option expected to provide meaningful benefit. For cutaneous melanoma: prior anti-PD-1/L1 (with or without antiCTLA-4) unless contraindicated; if BRAF V600-mutant, prior BRAF/MEK inhibitor therapy or documented unsuitability. For uveal melanoma: prior tebentafusp if HLA-A\*02:01-positive and eligible, or documented unsuitability/unavailability plus at least one prior systemic therapy.
* Tumor demonstrates CSPG4 and/or GD2 expression in archival or fresh tissue by central testing (suggested positivity threshold: at least 25% viable tumor cells by IHC or equivalent validated assay).
* At least 1 measurable lesion by RECIST v1.1.
* ECOG performance status 0-1.
* Adequate bone marrow, renal, hepatic, cardiac, and pulmonary function per protocol.
* Life expectancy of at least 12 weeks.
* Treated, stable brain metastases are allowed if neurologically stable for at least 4 weeks and not requiring escalating corticosteroids.
* Willingness to use effective contraception and comply with protocol-required visits, blood sampling, and requested biopsies.

Exclusion Criteria:

* Active symptomatic CNS metastases, leptomeningeal disease, or uncontrolled seizure disorder.
* Prior allogeneic stem cell transplant or solid organ transplant; prior gene-modified cellular therapy within 12 weeks; or anti-cancer therapy too close to lymphodepletion per protocol washout rules.
* Requirement for systemic immunosuppression greater than 10 mg prednisone equivalent/day or uncontrolled autoimmune/inflammatory disease requiring systemic treatment.
* Active uncontrolled infection, including uncontrolled HIV, HBV, or HCV, or fever/sepsis at the time lymphodepletion would begin.
* Clinically significant cardiovascular disease, uncontrolled arrhythmia, recent myocardial infarction, or uncontrolled thromboembolic disease.
* Grade 2 or higher unresolved toxicities from prior therapy, except stable endocrinopathy, alopecia, or vitiligo.
* Pregnancy or breastfeeding.
* Any condition that, in the investigator's judgment, would make lymphodepletion or CAR-NK infusion unsafe.