Clinical Study on the Safety and Efficacy of CAR-T/CAR-NK Cells in the Treatment of Recurrent Refractory or Unresectable Solid Tumors

To investigate the safety and efficacy of CAR-T/CAR-NK cells in patients with recurrent or unresectable solid tumors, including pancreatic cancer, prostate cancer, breast cancer, glioma, etc.

The study was divided into five stages: screening period, single harvest period, pretreatment chemotherapy period, treatment period, observation and follow-up period after treatment.

Subjects were pretreated with FC regimen before transfusion, and the subjects who met the infusion conditions were given CAR-T/CAR-NK cell infusion 1 ~ 2 days after the completion of eluent chemotherapy. The CAR-T/CAR-NK dose is calculated according to the patient's body weight, and the total number of cells transfused is about 1-2x106 /kg. Single intravenous infusion.

The efficacy was evaluated according to the evaluation criteria for solid tumors (RECIST1.1 selection).

Inclusion criteria

• Recurrent or unresectable solid tumors (including pancreatic, prostate, breast, glioma, etc.).
• Age over 15 and under 80.
• KPS≥50 or ECOG score ≤2 and expected survival greater than 3 months.
• No systemic therapy (except systemic immune checkpoint suppression or activation therapy) for at least 2 weeks or at least 5 drug half-lives (whichever is shorter) prior to apheresis.
• The absolute number of neutrophils was > 1.0x109 /L.
• Absolute number of platelets > 50x109 /L.
• Absolute number of lymphocytes ≥ 0.2x109 /L.
• ALT/AST < 3 times normal value.
• Total bilirubin < 1.5mg/dl.
• Creatinine < 2.5mg/dl, or creatinine clearance ≥60 mL/min/1.73 m2.
• The ejection fraction of heart ≥ 45%, echocardiography examination centerless fluid, electrocardiogram normal
• Blood oxygen saturation ≥92% under normal environment.
• Women of childbearing age who had a negative urine pregnancy test before dosing began and agreed to take effective contraception during the trial until the last follow-up visit.
• Volunteer to participate in this experiment and sign the informed consent.

Exclusion criteria

• 1) Those who are expected to survive less than 3 months. 2) Patients whose disease progression was so rapid that a complete treatment cycle could not be ensured at the time of enrollment as determined by the investigator.

• Patients with primary tumors other than melanoma skin cancer (unless cured for more than 3 years).

• Patients with infections including fungal, bacterial, viral or other uncontrolled infections or those requiring level 4 isolation.

• HIV, HBV, HCV positive patients. 6) Patients with central nervous system diseases including stroke, epilepsy, dementia or autoimmune central nervous system diseases.

• Myocardial infection, cardiac angiography or stenting, active angina pectoris or other significant clinical symptoms, or cardiogenic asthma or cardiovascular plasma cell infiltration in the 12 months prior to enrollment.

• Those who are receiving anticoagulation therapy or have severe coagulation dysfunction.

• The drug treatment that the patient is receiving will affect the safety and efficacy study of this project according to the judgment of the investigator.

• Patients with allergy or history of allergy to the biologics used in this project.

• Pregnant or lactating women. 12) Systematic use of systemic or systemic steroid drugs within 2 weeks prior to treatment (except those who have recently or currently used inhaled steroids).

• The efficiency of T cell transduction by replication-deficient lentivirus was less than 30%, or the ability to expand in response to CD3 / CD28 costimulatory signals was insufficient (<5 times).

• Those who have other uncontrolled diseases that the researchers consider unsuitable for enrollment.

• Any situation that the investigator believes may increase the risk to the subject or interfere with the test results.

• Patients who are also participating in other clinical studies.