Individualized Tumor Specific TCR- T Cells in the Treatment of Advanced Solid Tumors

Inclusion Criteria:

1. Aged between 18 and 70 years old, regardless of gender;
2. Diagnosed as solid tumors by histopathology, and the tumor lesions could be detected or evaluated;
3. Be after standard treatment or who lack effective treatment programs;
4. Patients and their families were willing to participate in the clinical trial and signed the informed consent;
5. Physical status: ECOG score 0-1;
6. Expected survival time \> 3 months;
7. HIV antibody negative;Hepatitis b surface antigen negative;Hepatitis c antibody negative;The results of blood routine and coagulation were roughly normal, lymphocyte \>0.8×10\^9/L, hemoglobin \>100g/L, and the pregnancy test of female patients with fertility potential was negative.
8. Left ventricular ejection fraction 50% as indicated by cardiac ultrasound;Upper normal level of serum ALT/AST \< 2.5 times;Serum creatinine 1.6mg/dl;Total bilirubin 1.5mg/dl, subject's total bilirubin \< 3mg/dl except for Gilberts Syndrome;
9. At least 4 weeks after the last systemic treatment, the patient's toxic and side effects must be restored to grade 1 or lower (except for alopecia or vitiligo).If the subject undergoes minor surgery within 3 weeks prior to enrollment, as long as all toxicity is recovered to level 1 or lower, the subject will meet the enrollment requirements.
10. During the whole study period, patients can regularly visit the enrolled research institutions for relevant detection, evaluation and management;
11. The patient is not allowed to use any anti-tumor drugs or treatments for 4 weeks prior to the infusion of TCR-T cells;
12. Patients' tumor lesions can be obtained by surgery or puncture, and tumor infiltrating T cells can be successfully isolated from the obtained tumor tissue;
13. T cells in patients' peripheral blood can effectively proliferate and expand by at least 10 times in the Pre-culture;
14. The benefits of participating in the clinical trial outweigh the risks,which was evaluated by the researchers base on the status or condition of the patients.

Exclusion Criteria:

1. Any form of primary immunodeficiency disease (such as severe combined immunodeficiency disease);
2. Experiencing moderate to severe infection or possible opportunistic infection;
3. Patients with a history of autoimmunity (e.g., SLE, psoriasis, etc.);
4. Acute systemic infection, coagulation dysfunction or other serious cardiopulmonary diseases;
5. Patients who have is suffering a large amount of glucocorticoid or other immunosuppressive agents within 4 weeks;
6. Be allergic to any drug used in this study;
7. Central nervous system metastases patients with clinically unstable or acute meningitis (except these clinically stable after treatment) Clinical stability needs to be met as follows: 4 weeks at least before the trial treatment, 1) no new brain lesion or no expanded of the original lesions confirmed by MRI); 2) no hormone therapy for at least 2 weeks; 3) neurological symptoms have returned to baseline;
8. Pregnant and lactating women, as well as male and female patients who could not cooperate with contraception during the study period.