Study on the Safety and Tolerability of PD-1 Knockout Tumor-infiltrating T Cells (TILs) in the Treatment of Advanced Colorectal Cancer

Inclusion Criteria: * Patients with advanced colorectal cancer confirmed by histology or cytology, who were not eligible to standard treatment at this stage. * Patients volunteered to receive surgery or biopsy to obtain tumor tissue for TILs preparation. * Aged ≥18 and ≤70 years old. * At least one tumor lesion that could be evaluated according to RECIST, version 1.1. * ECOG score was 0 or 1. * Adequate bone marrow and organ function. * The expected survival time of the enrolled patients was no less than 6 months. Exclusion Criteria: * Received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, traditional Chinese medicine with anti-tumor indications and other anti-tumor treatments within 2 weeks before sampling, except the following: 1. Nitrosourea or mitomycin C within 6 weeks before surgery; 2. Oral fluorouracils and small molecule targeted drugs for 1 week before surgery. * Received other unmarketed investigational drug or treatment within 4 weeks before sampling; * Had undergone major organ surgery (excluding needle biopsy) within 4 weeks before sampling or had significant lesions Trauma, or the need for elective surgery during the trial; * Received systemic glucocorticoid (prednisone \>10mg/ day or equivalent dose) or other immunosuppressive therapy within 14 days before sampling; Treatment with topical, ocular, intra-articular, nasal, and inhaled glucocorticoids was excluded. Short-term prophylaxis with glucocorticoids (e.g., to prevent contrast allergy) * Use of immunomodulatory drugs, including but not limited to thymosin, interleukin-2, interferin, etc., within 14 days before sampling; * Administration of live attenuated vaccine within 4 weeks before sampling; * The toxicity of previous antineoplastic therapy has not recovered to CTCAE 5.0 grade ≤1 (except for alopecia and other researchers who judged that there was no safety risk); * Patients with symptomatic central nervous system or leptomeningeal metastases or other evidence of uncontrolled central nervous system or leptomeningeal metastases as judged by the investigator to be ineligible for enrollment; * Patients with active infection within 1 week before sampling and currently requiring systemic anti-infective treatment; * A history of immunodeficiency, including positive HIV antibody test; * Hepatitis B (HBsAg positive and/or hepatitis C (anti-HCV positive) and/or treponema pallidum antibody positive; * Patients with current interstitial lung disease; * Has a history of severe cardiovascular and cerebrovascular diseases, including but not limited to: 1. severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, degree II-III atrioventricular block, etc. 2. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before the first dose of dose. 3. New York Heart Association (NYHA) functional class ≥II or left ventricular ejection fraction (LVEF) \<50%, or structural heart disease at high risk as judged by other investigators; 4. clinically uncontrolled hypertension. * Patients with active or previous autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), excluding patients with clinically stable autoimmune thyroid diseases and well-controlled type I diabetes; * Received immunotherapy with grade ≥ 3 irAE; * Clinically uncontrollable serous cavity effusion, which was judged by the investigator as not suitable for enrollment; * Known alcohol or drug dependence; * Persons with mental disorders or poor compliance; * Pregnant or lactating women;