Clinical Study on the Efficacy and Safety of CAR-DC in the Treatment of Advanced Solid Tumors

Clinical Study on the Efficacy and Safety of CAR-DC in the Treatment of Advanced Solid Tumors

This is a prospective, open label, single arm clinical trial to evaluate the safety and the preliminary efficacy of chimeric antigen receptor-dendritic cell (CAR-DC) in the treatment of advanced solid tumors positive for one of the following antigens: ephrin type-A receptor 2 (EphA2), claudin-18 isoform 2 (CLDN18.2) , trophoblast cell surface antigen 2 (Trop2), human epidermal growth factor receptor 2 (HER2), guanylyl cyclase-C (GCC), glypican-3 (GPC3) and carcinoembryonic antigen (CEA).

Dendritic cell (DC) plays a vital role in T cell priming and anti-tumor immune activation. A novel kind of engineered DC, chimeric antigen receptor-dendritic cell (CAR-DC) can reverse the immune suppression in tumor-microenvironment (TME) to enhance anti-tumor therapy. This is a prospective, open label, single arm clinical trial to evaluate the safety and the preliminary efficacy of CAR-DC in the treatment of advanced solid tumors positive for one of the following antigens: ephrin type-A receptor 2 (EphA2), claudin-18 isoform 2 (CLDN18.2) , trophoblast cell surface antigen 2 (Trop2), human epidermal growth factor receptor 2 (HER2), guanylyl cyclase-C (GCC) , glypican-3 (GPC3) AND carcinoembryonic antigen (CEA). A total number of 10 patients will receive two rounds of intravenous infusions of 30 million CAR-DC at an interval of 14 days and receive follow-up visits after the second round of infusion up to 1 or 2 years.

Inclusion Criteria:

1. Aged 18-70, regardless of gender;

2. Diagnosed as EphA2or Claudin18.2, TROP2, HER2, GCC, GPC-3, CEA positive advanced solid tumors, such as lung cancer, liver cancer, colorectal cancer, gastric cancer, etc; Note: Advanced solid tumors refer to locally advanced (stage III patients) and metastatic advanced (stage IV patients) TNM staging by the American Cancer Society (AJCC).

3. Immunohistochemical analysis of pathological tissue approves positive expression for one of the following antigens, including EphA2, Claudin18.2, TROP2, HER2, GCC, GPC-3 and CEA, with expression intensity ≥ 2+;

4. Failed response to standard treatment or unwilling/intolerant to all standard treatment regimens;

5. Imaging indicates measurable tumor lesions;

6. ECOG PS score: 0-2;

7. Expected survival time is greater than 3 months;

8. Maintaining good organ function and bone marrow reserve capacity:

   1. Bone marrow: Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L, platelet count ≥ 50 × 10^9/L, hemoglobin ≥ 80 g/L, and no blood transfusion or biological regulator treatments (such as granulocyte colony-stimulating factor, red blood cell growth factor, etc.) within 14 days prior to screening;
   2. Kidney: creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance rate (Ccr) ≥ 50 mL/min (according to the Cockcroft-Gault formula); Urine output>10 mL/h within 16-24 hours;
   3. Coagulation: International Normalized Ratio (INR) ≤ 1.5 × ULN, and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN (excluding those receiving therapeutic anticoagulants);
   4. Other: Blood oxygen saturation ≥ 90%, negative fecal occult blood test, etc.

9. The patient is willing to enroll and signs a written informed consent form, and is able to undergo diagnosis, treatment, and visits according to the protocol.

Exclusion Criteria:

1. Pregnant and lactating women; (The pregnancy test results are included in the CRF)
2. The patient can not guarantee effective contraceptive measures (such as condoms or birth control pills) within one year after enrollment;
3. Patients with brain metastases exhibiting significant psychiatric and neurological symptoms;
4. Serious heart diseases such as arrhythmia;
5. Autoimmune diseases;
6. Active bacterial, fungal, and other infections;
7. Infectious diseases: such as HIV, syphilis, tuberculosis, viral hepatitis and other diseases;
8. Patients are receiving medications such as glucocorticoids, thrombolytic drugs, and antipsychotic drugs;
9. Patients are believed not suitable for this clinical trial for other reasons by investigators.