This is a single-center, open-label, first-in-human, dose-escalation study in patients with pancreatic cancer.

A dose-escalation study will evaluate the safety, tolerability and efficacy of CAR-NK cells (CL-NK-001) in patients with locally advanced, metastatic, or recurrent pancreatic cancer.

Inclusion Criteria:

1. Aged 18-70 years;
2. Locally advanced, metastatic, or recurrent pancreatic cancer, with immunohistochemical detection of eGR1 (membrane positive tumor cell rate >40% and expression intensity ≥2+), who have failed, been intolerant to or reject standard treatment;
3. At least 1 measurable lesion according to RECIST 1.1;
4. Have not received anti-tumor treatment for at least 4 weeks;
5. ECOG performance status of 0-2;
6. Estimated life expectancy more than 12 weeks;
7. Hematology: neutrophils ≥ 1.5×10^9/L, lymphocytes ≥ 0.8×10^9/L, hemoglobin ≥ 100 g/L, and platelets ≥ 75 × 10^9/L;
8. Blood biochemistry: total bilirubin ≤ 2×ULN, alanine aminotransferase ≤ 3×ULN, aspartate aminotransferase ≤ 3×ULN, and creatinine clearance ≥ LLN (Cockcroft-Gault formula);
9. Volunteer to participate in this clinical study and willing to sign written informed consent.

Exclusion Criteria:

1. Evidence of central nervous system involvement;
2. Have received adoptive cell therapy;
3. Patients with any uncontrolled active infection, including but not limited to: HBV, HCV, HIV, or treponema pallidum serology positive;
4. Vaccinated with a live attenuated vaccine within 3 months;
5. History of immunodeficiency;
6. Active autoimmune disease;
7. Have severe conditions, including but not limited to: (1) severe respiratory diseases; (2) severe cardiovascular diseases (previous history of CABG/PCI; myocardial infarction/unstable angina pectoris, congestive heart failure of NYHA III-IV, left ventricular ejection fraction < 50%, or poorly controlled hypertension within 6 months; QTc interval > 480ms, long or short QT syndrome; previous history of ventrical arrhythmia, or ventrical arrhythmia under anti-arrhythmic drugs/ICD); (3) poorly controlled diabetes and other metabolic diseases; (4) severe gastrointestinal diseases (severe gastrointestinal bleeding, severe diarrhea of CTCAE ≥ 2, or severe gastrointestinal obstruction needing intervention);
8. Possible severe adverse events, allergy or other contraindications to drugs or its component under study;
9. Pregnant or lactating women;
10. History of neurological or psychological disorders;
11. Not suitable to participate this clinical study judged by the investigator.