KRAS G12D-specific Immune Effector Cells Targeting KRAS G12D-positive Solid Tumors

Inclusion Criteria:

1. Abilities to understand and the willingness to provide written informed consent;
2. ≥ 18 and ≤ 75 years old;
3. Histologically confirmed recurrent, refractory or metastatic advanced malignancies with documented KRAS G12D somatic mutation and measurable lesions by RECIST v1.1; patients have progressed after at least one line of standard of care systemic therapy for their malignancy. At time of leukapheresis, patients are either off dexamethasone or receiving dexamethasone ≤ 4 mg/day;
4. ECOG performance status 0-2 (or Karnofsky performance score ≥ 60);
5. Life expectancy >3 months;
6. Satisfactory bone marrow, liver and kidney functions as defined by the following: absolute neutrophile count ≥ 1500/mm^3; hemoglobin > 10 g/dL; platelets > 100000 /mm^3; Bilirubin < 1.5×ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5×ULN; creatinine < 1.5×ULN;
7. Peripheral blood absolute lymphocyte count must be above 0.8×10^9/L;
8. Satisfactory heart functions;
9. Must be willing to follow the instructions of doctors;
10. Women of reproductive potential (between 15 and 49 years old) must have a negative pregnancy test within 7 days of study start. Male and female patients of reproductive potential must agree to use birth control during the study and 3 months post study.

Exclusion Criteria:

1. Receipt of KRAS G12D based therapy within 8 weeks prior to study entry;
2. HIV positive;
3. Tuberculosis infection not under control;
4. History of autoimmune disease, or other diseases requiring long-term administration of steroids or immunosuppressive therapies;
5. History of allergic disease, or allergy to immune cells or study product;
6. Patients already actively enrolled in other immune cell clinical study;
7. Presence of untreated or actively progressing central nervous system metastases not locally controlled;
8. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.