TCR-T Cell Therapy on Advanced Solid Tumors

Inclusion Criteria：

1. Age greater than 18 years old；
2. Subjects with advanced solid tumors confirmed by histology/cytology who have failed standard treatment, are intolerant to standard treatment, or for whom no standard treatment exists. . Non-small cell lung cancer: Recurrent/metastatic non-small cell lung cancer previously treated with platinum-based chemotherapy and/or immunotherapy and/or anti-angiogenic therapy; ii. Pancreatic cancer: Recurrent/metastatic pancreatic cancer that has failed at least one prior systemic therapy; iii. Colorectal cancer: Recurrent/metastatic colorectal cancer that has failed at least two prior systemic therapies (including oxaliplatin, irinotecan, fluoropyrimidine-based agents, anti-angiogenic drugs, etc.); iiii. Other tumors: Other advanced solid tumors that have failed standard treatment, are intolerant to standard treatment, or for which no standard treatment exists;
3. Previous tissue pathology or peripheral blood testing confirmed the presence of KRAS G12V or G12D mutations with matching HLA subtypes；
4. Expected survival duration of more than 3 months；
5. Eastern Cooperative Oncology Group( ECOG )score ≤2；
6. All participants voluntarily participate in this study and sign an informed consent. And the subjects have good compliance and can cooperate with investigators follow-up study.
7. Patients at least have had at least one measurable lesion as defined by RECIST v1.1 criteria；
8. Female participants can not be pregnant or lactating and their serum or urine human chorionic gonadotropin tests must be negative within 72 hours prior to study enrollment；All subjects must be using a medically accepted means of contraception ( (e.g., oral contraceptives, intrauterine device) during the course of this study and for at least 3 months after completion of study therapy.
9. Organ function and bone marrow reserve are in good condition, and the following requirements must be met:

1)Absolute neutrophil count≥1.5×10⁹/L, Absolute lymphocyte count ≥0.5×10⁹/L；2)Platelet count≥50×10⁹/L；3)Hemoglobin≥90g/L；4)Bilirubin \< 1.5 times upper limit of normal（Bile duct obstruction due to tumor compression were excluded)；5)Serum creatinine ≤ 1.5 times the upper limit of normal range or creatinine clearance ≥ 60 mL/min.6)Serum alanine aminotransferase or aspartate aminotransferase is \< 2.5 times the upper limit of the normal value (ULN) (if patients with liver metastasis, ≤5 times the ULN).7)Coagulation function normalised：INR≤1.5，PTT\<1.2 times the upper limit of normal（Tumor - related anticoagulant therapy was excluded).

Exclusion Criteria:

1. Intracranial metastasis or Patients with moderate or severe hydrothorax need drain placement to relieve symptoms.
2. Active pulmonary tuberculosis
3. Human immunodeficiency virus (HIV) positive；
4. Active Hepatitis B or Hepatitis C infection；
5. Pregnant women and lactating females；
6. Previous or concurrent history of other malignant tumors. Exceptions include curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy;
7. Patients with central nervous metastases；
8. Serious, uncontrolled comorbidities that may affect protocol compliance or interfere with interpretation of results，or any serious medical condition that may affect the safety of the subjects ;
9. History of clinically significant respiratory diseases or other respiratory diseases that seriously affect Pulmonary function;
10. Any active autoimmune disease,any condition requiring steroid hormones or immunosuppressive therapy( including but not limited to systemic lupus erythematosus, sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc., require \> 10 mg/D of prednisone or equivalent hormone）
11. A history of organ transplantation；
12. A history of myocardial infarction and severe arrhythmia within six months；Ineligible also includes uncontrolled hypertension, coronary heart disease, stroke, liver cirrhosis, nephritis and other serious complications;
13. Those who have a history of psychotropic drug abuse and cannot quit or have a history of psychiatric impairment；
14. Participants with an allergic constitution, known sensitivity to human serum albumin, cyclophosphamide, fludarabine and interleukin 2;
15. Those with bleeding or thromboembolic tendency：bleeding symptoms of clinical significance or a clear tendency to bleeding within 2 weeks prior to entering the study. And those with hereditary or acquired bleeding and thrombotic tendencies； serious arterial/venous thromboembolic events occurred in the previous 6 months;
16. Other severe, acute or chronic medical or mental illnesses that in the investigator's judgement will might be increase the risk associated with the patient's participation in the study or interfere with interpretation of research results.