Interventional Therapy Sequential With the Fourth-generation CAR-T Targeting Nectin4/FAP for Malignant Solid Tumors

According to the high expression of tumor cell-associated antigen Nectin4 in patients with solid tumors such as non-small cell lung cancer, breast cancer, ovarian cancer, bladder cancer, and pancreatic cancer, and in order to target FAP-positive CAFs in the tumor-associated stroma, the Intravenous minimally invasive surgery combined with intratumoral injection of Nectin4/FAP-targeted fourth-generation CAR-T cells (expressing IL7 and CCL19, or IL12) are used to treat Nectin4-positive advanced malignant solid tumors, maximally eliminating residual cancer cells and preventing recurrence.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

1. Patients who meet the requirements voluntarily participate in the study and sign the Informed Consent Form.
2. Age is 18 to 75 years old, gender is not limited; the Eastern Cancer Cooperative Group (ECOG) scores 0 to 3
3. Pathological diagnosis of malignant solid tumors.
4. Advanced malignant solid tumors meet the CSCO malignant tumor diagnosis and treatment guidelines (2018 version). (Flow or pathology shows that tumor cells express Nectin4 antigen and tumor-associated fibroblasts express FAP antigen)
5. Head magnetic resonance or CT examination showed no central invasion of malignant tumors.
6. Collection of peripheral blood mononuclear cells must be more than 2 weeks from radiotherapy and chemotherapy.
7. Peripheral blood neutrophils number ≥ 1000 / μl, platelets ≥ 50,000 / μl.
8. Heart, liver and kidney function: creatinine \<2.5mg/dl; ALT (alanine aminotransferase) / AST (aspartate aminotransferase) \<3 times lower than the upper limit of normal; total bilirubin \<2.0mg/dl.
9. Cardiac ejection fraction (EF) ≥ 50%, echocardiography without pericardial effusion.
10. Have fertility must be willing to use contraceptive methods.
11. The expected survival period is more than 12 weeks.
12. No other malignant tumors, severe autoimmune diseases or congenital immunodeficiency, serious progressive infection, cranial nerve disorder or mental illness.

Exclusion Criteria:

1. Pregnant or lactating women.
2. Patients with uncontrollable active infections.
3. Patients with systemic steroids; recent or current use of inhaled steroids is not excluded.
4. Previously involved CAR-T cell therapies produced any uncontrolled disease.

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