Exploratory Clinical Study of Targeted Activated DC and CAR-T Therapy in Advanced Solid Cancers

Inclusion criteria

• Age ≥ 18 years and ≤ 75 years, regardless of gender;
• Advanced solid tumors with clear pathological confirmation, including but not limited to gastric cancer, colorectal cancer, pancreatic cancer, prostate cancer, etc.; at least one measurable lesion meeting RECIST 1.1 criteria (according to RECIST 1.1, the longest diameter of a measurable lesion on spiral CT scan ≥ 10 mm, or the short diameter of a pathological lymph node ≥ 15 mm);
• Tumor tissue positive for Claudin 18.2, GCC, TROP2, or PSMA targets by immunohistochemistry (IHC) (expression intensity ≥ 2+; percentage of positive cells ≥ 40%);
• Meets the indications for PBMC collection and has no contraindications for cell collection;
• Failure of standard second-line treatment, or lack of a standard treatment regimen; or refusal to receive chemotherapy (with signed documentation);
• ECOG performance status: 0-1;
• Life expectancy: ≥ 3 months;
• Toxicities from prior chemotherapy or other anti-tumor therapies must have resolved after a washout period (except for residual alopecia), ensuring that all organ functions meet the inclusion criteria;
• Adequate organ function, including:

• Adequate immune function: absolute lymphocyte count (ALC) ≥ 0.5 × 10⁹/L, absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L, monocyte count ≥ 0.1 × 10⁹/L.
• Adequate hematopoietic function: platelet count ≥ 75 × 10⁹/L, hemoglobin ≥ 90 g/L. Patients must not have received blood transfusions or treatments such as granulocyte colony-stimulating factor, thrombopoietin, or erythropoietin within 14 days prior to the blood count assessment.
• Adequate liver function: total bilirubin (TBIL) < 2 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × ULN.
• Adequate renal function: creatinine (Cr) ≤ 1.5 × ULN.
• Adequate coagulation function: prothrombin time (PT) or activated partial thromboplastin time (APTT) < 1.5 × ULN, and international normalized ratio (INR) < 1.5.
• Individuals of childbearing potential must agree to use effective contraception during the study;
• Ability to understand and willingness to sign a written informed consent form;
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion criteria

• Oncological emergencies requiring immediate intervention, such as malignant pericardial effusion or tamponade, superior vena cava syndrome, or spinal cord compression;
• Significant cardiovascular disease, including:

• Documented major cardiovascular events within the past 6 months, such as myocardial infarction, angina pectoris, heart failure, severe arrhythmia, or prior angioplasty, stent implantation, or coronary artery bypass grafting;
• Clinically significant QT interval prolongation (QTcF > 470 ms for women or QTcF > 450 ms for men);
• Clinically significant bleeding tendency or coagulation disorders (e.g., hemophilia);
• Active infection with HIV, syphilis, hepatitis B virus (HBV), or hepatitis C virus (HCV);
• History of involuntary commitment due to mental illness, or any psychiatric condition deemed by the investigator to make the patient unsuitable for the trial;
• Concurrent autoimmune diseases, or long-term use of immunosuppressants or systemic corticosteroids;
• Poor compliance, as assessed by the investigator;
• Prior treatment with any targeted CAR-T cell therapy within 3 months before this CAR-T infusion;
• Uncontrolled active bacterial or fungal infections;
• Any other condition that, in the opinion of the investigator, makes the patient ineligible for the study.