TP53 R248Q TCR-T Cell Therapy for Advanced Solid Tumor

Inclusion Criteria:

1. signed a written informed consent form (ICF), and can comply with protocol-specifiedvisits and related procedures;

2. aged ≥ 18 years, and ≤ 75 years, male or female;

3. Subject must be pathologically confirmed with one of the histology below: Lung carcinoma Colorectal adenocarcinoma Pancreatic adenocarcinoma Any other solidtumor (progression after receiving standard treatment);

4. subjects with TP53R248Q mutation in genetic testing, as determined by DNA or RNAsequencing methods;

5. if patients with brain metastases are asymptomatic and less than 3 brain lesionsless than 3 cm in diameter, they may be eligible;

6. ECOG score 0-1;

7. Expected survival of no less than 12 weeks;

8. According to RECISTv1.1 and mRECIST, subjects have at least 1 measurable lesion (lesions that have received local therapy such as radiotherapy and interventionaltherapy cannot be used as measurable lesions unless imaging evidence confirms thatthe lesion has clearly progressed), RECISTv1.1 is non-lymph node lesions with thelongest diameter ≥ 10 mm on CT or MRI, and/or lymph node lesions with the shortdiameter ≥ 15 mm; mRECIST is non-lymph node measurable lesion criteria that meetRECISTv1.1 criteria, and showed intratumoral arterial enhancement in enhanced CT orMRI;

9. subjects should provide fresh tumor tissue samples that meet the requirements orwithin 2 years before signing the ICF;

10. Adequate organ and bone marrow function as defined by the following laboratorycriteria: (1) bone marrow function: absolute neutrophil count (ANC) ≥ 1.5 × 109/L;platelet (PLT) ≥ 75 × 109/L (transfusion or hematopoietic stimulating factor notacceptable within 14 days prior to Screening); (2) hemoglobin ≥ 90 g/L; (3) liverfunction: total bilirubin ≤ 2.5 × ULN; alanine aminotransferase ≤ 5 × ULN; aspartateaminotransferase ≤ 5 × ULN; (4) renal function: serum creatinine ≤ 1.5 × ULN, orcreatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula); (5)coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, activatedpartial thromboplastin time (APTT) ≤ 1.5 × ULN (INR between 2.0 and 3.0 is requiredfor subjects receiving prophylactic anticoagulant therapy);

11. Males of childbearing potential and females of childbearing potential must agree touse effective contraception from signing the ICF until one year after the last cellinfusion and females of childbearing potential must have a negative blood pregnancytest at screening.

Exclusion Criteria:

1. previous bone marrow or organ transplantation (including but not limited to livertransplantation) or waiting for transplantation;

2. previous or concurrent history of other malignancies (cured and at least 2 yearsbefore screening without recurrence of cervical carcinoma in situ, non-invasivebasal cell or squamous cell skin cancer or radical treatment of local prostatecancer, 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) positiveand HBV DNA > 500 IU/mL (lower limit of detection < HBV DNA ≤ 500 IU/mL, clearlymphocyte conditioning medication before the need for at least 14 days of antiviraltherapy and continuous antiviral therapy during the study can be enrolled);hepatitis C virus (HCV) antibody positive and HCV RNA positive; humanimmunodeficiency virus (HIV) antibody positive; syphilis antibody positive;

4. HLA antibody positive subjects, including weak positive, positive and strongpositive (those with different HLA typing sites from TP53R248QTCR-T cell injectioncan 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 targeteddrugs within 14 days or 5 half-lives (whichever is shorter) before screening, andany 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 relievesymptoms); traditional Chinese medicine/Chinese herbal medicine and localinterventional therapy with antineoplastic indications within 14 days beforescreening;

7. adverse events caused by previous antineoplastic therapy have not yet recovered tograde 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 attenuatedvaccination 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 orequivalent) or other immunosuppressive medication within 14 days prior to the firststudy drug infusion or during the study, with the exception of inhaled or topicaluse;

11. Subjects with fungal, bacterial, viral, tuberculosis or other infection requiringsystemic anti-infective therapy within 14 days prior to screening;

12. Patients with active or previous autoimmune diseases that may relapse, such assystemic 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, suchas pleural effusion and ascites that cannot be controlled by drainage or othermethods;

15. History of serious cardiovascular and cerebrovascular diseases, including but notlimited to:

• severe heart rhythm or conduction abnormalities, such as ventricular arrhythmiarequiring clinical intervention, grade II-III atrioventricular block, etc.;

• prolonged QT interval corrected by Fridericia formula (QTcF), > 450 ms inmen and > 470 ms in women;

• acute coronary syndrome, congestive heart failure, aortic dissection, stroke orother ≥ Grade 3 cardiovascular and cerebrovascular events within 6 monthsbefore screening;

• presence of heart failure with New York Heart Association (NYHA) functionalclass ≥ II or left ventricular ejection fraction (LVEF) < 50%;

• clinically uncontrolled hypertension, systolic blood pressure ≥ 160 mmHg and/ordiastolic blood pressure ≥ 100 mmHg.

16. Patients with a history of pulmonary embolism or severe lower extremity deep venousthrombosis, need to undergo inferior vena cava filter placement and otherinterventional therapy or need to use therapeutic doses of anticoagulants duringscreening;

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 complianceor are not suitable for participating in this study.