pd-1 antibody expressing car t cells for mesothelin positive advanced malignancies

Conditions: Solid Tumor, Adult; Advanced Cancer

Summary: this is a single-arm, open-label, one center, dose escalation clinical study, to determine the safety and efficacy of infusion of autologous t cells engineered to express immune checkpoint antibody and chimeric antigen receptor targeting mesothelin in adult patients with mesothelin positive, recurrent or refractory malignant tumors.


Eligibility criteria:
inclusion criteria: * 1. relapsed or refractory advanced solid malignancies. * 2. progressive disease and no response to current therapy. * 3. patients must have previously received at least one standard therapy for their cancer (if available) and have been either non-responders (progressive disease) or have recurred. and patients are willing to attend the clinical trial. * 4. gender unlimited, age from 18 years to 80 years. * 5. life expectancy≥6 months. * 6. ecog (eastern cooperative oncology group) performance status of 0-2. * 7. adequate venous access for apheresis, and no other contraindications for leukapheresis ; peripheral venous access ；no contraindication of lymphocyte separation. * 8. ihc( immuno-histochemistry) result of tumor tissue： mesothelin positive for ：frequency≥2，intensity≥2 +. the percentage of tumor cell nuclei stained (0, no staining; 1, ≤10%; 2, 10-50% and 3, \>50%) and the staining intensity (ranging from 0 to 3+). * 9. adequate hepatic function, renal function and bone marrow function：wbc≥3.0×109/l,plt≥60×109/l,hgb≥85g/l,ly≥0.7×109/l; alanine aminotransferase/aspartate transaminase(alt/ast) 2.5 times the upper limit of the normal value, total bilirubin(tbil) 1times the upper limit of the normal value, serum creatinine1.5 times the upper limit of the normal value. * 10. willing and able to understand and sign the informed consent document. * 11. women of child-bearing age must have evidence of negative pregnancy test. patients must be willing to practice birth control during and for four months following treatment. exclusion criteria: * 1. life expectancy6 months. * 2. patients with uncontrolled active infection will be excluded. * 3. patients with severe heart and lung dysfunction; uncontrolled hypertension, unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (\> new york heart association class ii), or myocardial infarction within 6 months of study will be excluded; aberrant pulmonary function testing: with a forced expiratory volume (fev) of \<30%(predicted), diffusion capacity of the lung for carbon monoxide (dlco) (corrected) \<30% and oxyhemoglobin saturation90% will be excluded. * 4. patients with severe liver and kidney dysfunction or chronic diseases of important organs will be excluded. * 5. patients with active autoimmune disease requiring immunosuppressive therapy will be excluded. * 6. patients requiring corticosteroids (other than inhaled) will be excluded. * 7. patients with other severe diseases or situations improper for the research will be excluded, including neurologic disease, mental disease, immune disease, metabolic disease, and contagious disease. * 8. pregnant and/or lactating women will be excluded. * 9. patients who have had other bio-therapy in the past 4 weeks. * 10. patients who are participating or participated any other clinical trials in latest 30 days will be excluded. * 11. patients with the subject suffering disease affects the understanding of informed consent or complying with study protocol will be excluded.

Keywords: mesothelin pd-1 car t solid tumor