ny-eso-1 tcr-t cells for ny-eso-1 positive subjects with advanced solid tumors

Conditions: Advanced Solid Tumors

Summary: new york esophageal squamous cell carcinoma 1 (ny-eso-1) is a cancer-testis antigen (cta) which is expressed in various tumors. in tcr-t therapy, researchers take the blood of a certain patient, select t cells and insert genes into the cell that expressing a kind of protein that targeting ny-eso-1. the genetically engineered cells are called ny-eso-1 tcr-t cells. then the engineered cells are re-infused to the cancer patients to cure the disease or prolong life.

this is a single-center, open-label, phase i clinical study of tcr-t cells for the treatment of the recurrent/metastatic solid tumors patients who had failed standard therapy. objective: to evaluate the safety and efficacy of tcr-t cells for the treatment of advanced solid tumors. eligibility: adults aging 18-70 with advanced solid tumors design: patients will undergo screening tests, including imaging procedures, heart and lung tests, and lab tests. patients will have leukapheresis. blood will be removed through a needle in the arm. a machine separates the white blood cells. the rest of the blood is returned through a needle in the other arm. engineered t cells will be re-infused into the patient. patients will stay in hospital and be evaluated

Eligibility criteria:
inclusion criteria: * be able to understand and sign the informed of consent document. be willing to follow the procedure and protocol of the clinical trial; * age ≥ 18 years and ≤ 70 years; * expected survival time \> 3 months; * ecog score 0-1; * metastatic or recurrent solid tumors confirmed by histopathology; * refractory to standard treatment evaluated by radiological assessment; * be able provide fresh or preserved tissue specimen; * at least 1 measurable lesion (according to recist 1.1); * ny-eso-1 expression positive: immunohistochemical staining positive cells ≥25% and positive staining intensity is "++" or above; * hla typing is hla-a2 (excluding hla-a\*0203); * hematology should at least meet the following criteria: 1. absolute neutrophil count (anc) ≥ 1.5× 109/l (±20%)； 2. platelet (plt） ≥ 75× 109/l (±20%）； 3. hemoglobin (hgb) ≥ 90 g/l (±20%). * liver and kidney function are normal: 1. serum creatinine (cr) ≤ 1.5 times of upper limit of normal (uln) or creatine clearance ≥ 60 ml/min; 2. serum alanine aminotransferase (alt) or/and aspartate aminotransferase (ast) ≤ 2.5 times of upper limit of normal; 3. total bilirubin (tbil) ≤ 15 times of upper limit of normal. * blood coagulation function is normal: prothrombin time (pt) ≤ 1.5 uln, international normalized ratio (inr) ≤ 1.5 uln, or activated partial thromboplastin time (aptt) ≤ 1.5 uln; * echocardiogram results show: left ventricular ejection fraction \>45%; * women of childbearing potential should be ascetic or take contraception since the signing of icf to 24 weeks or later after the last administration of drug note: women of childbearing age who have undergone surgical sterilization or who have already experienced menopause are considered to have no possibility of pregnancy. * before the tc-n201 injection was reconstituted, the toxic effects of standard treatment had already recovered, and the corresponding adverse events were judged by the researcher to not pose a safety risk; * catheter insertion is feasible and no white blood cells collection contraindications. exclusion criteria: * under pregnancy or lactation, or positive based on blood pregnancy test; * severe allergic to related ingredients in the clinical trial; * received any other investigational treatment within 4 weeks before the first administration or enrolled in another clinical trial the same time; * history of other known malignant tumors within the previous 5 years, including carcinoma in situ of the cervix, basal cell carcinoma of the skin, and carcinoma in situ of the prostate; except for localized tumors that have been cured; * primary central nerve system (cns) cancer, or subjects with cns metastasis after localized treatment; * subjects with any active autoimmune disease, a history of autoimmune disease, or a history or syndrome requiring treatment with systemic steroids or immunosuppressive drugs; * immunodeficiency including hiv positive, harvested or natural immunodeficiency; * subjects with ≥ grade 3 thromboembolic events within 2 years or under thrombolysis treatment; * subjects with hereditary or acquired hemorrhagic disease; * have clinical cardiovascular disease or symptoms; * subjects with active infection: active infection requiring systemic anti-infective treatment (except topical antibiotics), fever caused by cancer could be enrolled according to the investigator's judgment; * subjects with active pulmonary tuberculosis infection detected by medical history or computed tomography (ct), or a history of active pulmonary tuberculosis infection within 1 year before enrollment, or a history of active pulmonary tuberculosis infection more than 1 year before enrollment but without regular treatment; * subjects with positive hepatitis b surface antigen or positive hepatitis b core antibody or positive hepatitis c virus antibody; * treponema pallidum antibody positive; * subjects received major surgery or under severe injury within 4 weeks before tc-n201 cell infusion; * subjects who received live vaccine or attenuated live vaccine 28 days before leukapheresis; * subjects who have drug addiction history, or alcoholism, drug users; * subjects who received cell therapy before enrollment，such as tcr-t，car-t and til; * subjects who have previously received treatment targeting ny-eso-1; * subjects not suitable for the clinical trial according to investigators.