Dual-Targeting CAR-NK Cells in Biomarker-Selected Advanced Colorectal Cancer

Inclusion Criteria:

* Histologically confirmed colorectal adenocarcinoma that is unresectable or metastatic and has progressed after, is intolerant to, or is ineligible for standard therapies.
* Measurable disease per RECIST v1.1 (unless in minimal residual disease (MRD) or post-resection cohorts if a future amendment is planned).
* Tumor antigen co-expression meeting central lab thresholds for one of the following pairs: CEA+GUCY2C, CEA+HER2, or GUCY2C+HER2.
* ECOG performance status 0-1.
* Adequate organ function (hematologic, renal, hepatic, and cardiac) as defined in protocol.
* Recovered to Grade ≤1 from prior therapy-related toxicities (except stable Grade 2 neuropathy or alopecia).
* Life expectancy ≥ 12 weeks.
* Willingness to use effective contraception during study and for a protocol-defined period after cell infusion.

Exclusion Criteria:

* Active, uncontrolled infection (including uncontrolled HBV/HCV) or known uncontrolled HIV infection.
* Active CNS metastases that are symptomatic or require escalating steroids. (Stable treated CNS disease may be allowed per protocol.)
* Prior gene-modified cellular therapy (CAR-T/CAR-NK/TCR-T) within 6 months, or any prior therapy that in the investigator's judgment increases risk of severe toxicity.
* Clinically significant autoimmune disease requiring systemic immunosuppression within the past 6 months.
* Concurrent anti-cancer therapy (other than protocol-permitted bridging) during the DLT window.
* Pregnant or breastfeeding.
* Significant cardiovascular disease (e.g., recent MI, uncontrolled arrhythmia), uncontrolled pulmonary disease, or other severe comorbidity that would increase risk.
* Known hypersensitivity to study chemotherapy components (fludarabine/cyclophosphamide) or required supportive medications.
* Any condition that, in the investigator's opinion, would interfere with study participation, safety monitoring, or interpretation of results.