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

This study is an open, single-center, phase I clinical trial which is aim to evaluate the safety and tolerability of tumor-specific TCR-T cells. In this study, these TCR-T cells will be multiplied, or grown, in the laboratory.Subjects will received TCR-T cells infusions twice at day 0 and day 14, with the use of IL-2 for 5 consecutive days after every cell infusion.

Inclusion criteria

• Aged between 18 and 70 years old, regardless of gender;
• Diagnosed as solid tumors by histopathology, and the tumor lesions could be detected or evaluated;
• Be after standard treatment or who lack effective treatment programs;
• Patients and their families were willing to participate in the clinical trial and signed the informed consent;
• Physical status: ECOG score 0-1;
• Expected survival time > 3 months;
• 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.
• 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;
• 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.
• During the whole study period, patients can regularly visit the enrolled research institutions for relevant detection, evaluation and management;
• The patient is not allowed to use any anti-tumor drugs or treatments for 4 weeks prior to the infusion of TCR-T cells;
• Patients' tumor lesions can be obtained by surgery or puncture, and tumor infiltrating T cells can be successfully isolated from the obtained tumor tissue;
• T cells in patients' peripheral blood can effectively proliferate and expand by at least 10 times in the Pre-culture;
• 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

• Any form of primary immunodeficiency disease (such as severe combined immunodeficiency disease);
• Experiencing moderate to severe infection or possible opportunistic infection;
• Patients with a history of autoimmunity (e.g., SLE, psoriasis, etc.);
• Acute systemic infection, coagulation dysfunction or other serious cardiopulmonary diseases;
• Patients who have is suffering a large amount of glucocorticoid or other immunosuppressive agents within 4 weeks;
• Be allergic to any drug used in this study;
• 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;
• Pregnant and lactating women, as well as male and female patients who could not cooperate with contraception during the study period.