TP53 R248Q TCR-T Cell Therapy for Advanced Solid Tumor

Exclusion Criteria

• •1. previous bone marrow or organ transplantation (including but not limited to liver transplantation) or waiting for transplantation;
• •2. previous or concurrent history of other malignancies (cured and at least 2 years before screening without recurrence of cervical carcinoma in situ, non-invasive basal cell or squamous cell skin cancer or radical treatment of local prostate cancer, radical resection of ductal carcinoma in situ can be enrolled in the study);
• •3. hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and HBV DNA \> 500 IU/mL (lower limit of detection \< HBV DNA ≤ 500 IU/mL, clear lymphocyte conditioning medication before the need for at least 14 days of antiviral therapy and continuous antiviral therapy during the study can be enrolled); hepatitis C virus (HCV) antibody positive and HCV RNA positive; human immunodeficiency virus (HIV) antibody positive; syphilis antibody positive;
• •4. HLA antibody positive subjects, including weak positive, positive and strong positive (those with different HLA typing sites from TP53R248QTCR-T cell injection can be enrolled in the study);
• •5. previous treatment with other cell products or TP53 targeted drugs;
• •6. treatment with any fluorouracil chemotherapeutic drugs or small molecule targeted drugs within 14 days or 5 half-lives (whichever is shorter) before screening, and any antineoplastic biological agents or non-fluorouracil chemotherapeutic agents; radical radiotherapy or extensive radiotherapy within 28 days before screening (except palliative radiotherapy for non-target lesions performed locally to relieve symptoms); traditional Chinese medicine/Chinese herbal medicine and local interventional therapy with antineoplastic indications within 14 days before screening;
• •7. adverse events caused by previous antineoplastic therapy have not yet recovered to grade 1 or baseline levels, except for alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stabilized by hormone replacement therapy;
• •8. live attenuated vaccination within 28 days before screening, or live attenuated vaccination during the study;
• •9. major surgical treatment (except liver mass biopsy) within 28 days before screening, or major surgical treatment during the study;
• •10. Requirement for chronic systemic corticosteroids (at doses ≥ 10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days prior to the first study drug infusion or during the study, with the exception of inhaled or topical use;
• •11. Subjects with fungal, bacterial, viral, tuberculosis or other infection requiring systemic anti-infective therapy within 14 days prior to screening;
• •12. Patients with active or previous autoimmune diseases that may relapse, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis, psoriasis, etc.;
• •13. Previous or current interstitial lung disease, dust disease, radiation pneumonitis, severely impaired pulmonary function and other conditions;
• •14. Third space effusion that is not clinically well controlled before screening, such as pleural effusion and ascites that cannot be controlled by drainage or other methods;
• •15. History of serious cardiovascular and cerebrovascular diseases, including but not limited to:
• •* severe heart rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, grade II-III atrioventricular block, etc.;
• •* prolonged QT interval corrected by Fridericia formula (QTcF), \> 450 ms in men and \> 470 ms in women;
• •* acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other ≥ Grade 3 cardiovascular and cerebrovascular events within 6 months before screening;
• •* presence of heart failure with New York Heart Association (NYHA) functional class ≥ II or left ventricular ejection fraction (LVEF) \< 50%;
• •* clinically uncontrolled hypertension, systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg.
• •16. Patients with a history of pulmonary embolism or severe lower extremity deep venous thrombosis, need to undergo inferior vena cava filter placement and other interventional therapy or need to use therapeutic doses of anticoagulants during screening;
• •17. Subjects are participating in other interventional clinical studies;
• •18. Pregnant or lactating women;
• •19. Researchers believe that subjects have other conditions that may affect compliance or are not suitable for participating in this study.