clinical study on the treatment of malignant brain glioma by qh104 cell injection

Conditions: Brain Gliomas

Summary: this is a study on the clinical application of chimeric antigen receptor modified γδ t cells (car-γδ t cells) in relapsed and refractory b7h3 positive malignant brain glioma.the main purpose of this study was to evaluate the safety and feasibility of car-γδ t cell infusion in patients with relapsed and refractory b7h3 positive malignant brain glioma.

γδt cells are known as "a great candidate for car-t cells". although they only account for 2% - 5% of all t cells in our body, they are a natural killer. treatment on this study includes six b7h3 car-γδ tcell infusions over an 12 week period. b7h3 car-γδ t cells will be locoregionally administered via a cns reservoir catheter without lymphodepleting chemotherapy. the study will evaluate the safety, feasibility and maximum tolerated dose (mtd) of b7h3 car-γδ t cell using a 3+3 study design and an 4 week evaluation period. the total study duration will be 2 years.

Eligibility criteria:
inclusion criteria: * 1)age 18-70 years old (both ends included), both male and female; * 2)at least one evaluable lesion with previous biopsy or pathohistologic confirmation of high-grade glioma (who grade iv), with imaging suggestive of continued progression or recurrence after comprehensive treatment; * 3) surgically resected pathological tissue capable of being used for immunohistochemical detection of target proteins and positive for b7h3 expression; * 4) kps ≥ 60 points; * 5)expected survival \> 3 months; * 6)substantially normal bone marrow reserve function and normal liver and renal function (laboratory tests need to be fulfilled before receiving qh104 cell injection for the first time):white blood cell count (wbc) ≥ 3 x 109/l;lymphocyte count (ly) ≥ 0.8 x 109/l;hemoglobin (hb) ≥ 90g/l;platelet (plt) ≥80×109/l;albumin transaminase (alt) \& albumin transaminase (ast) \<1.5×uln;serum creatinine (cr) \<1.5 x uln;total bilirubin \< 1.5 x uln;pt \& ptt ≤ 1.25 x uln. * 7)no obvious hereditary diseases; * 8)normal cardiac function with cardiac ejection index \>55%; * 9)no bleeding and coagulation disorders; * 10)women of childbearing age (15-49 years old) must have had a pregnancy test with a negative result within 7 days prior to the start of treatment, and subjects are willing to use contraception during the clinical trial and for 3 months after the last cell infusion; * 11) sign the informed consent form. exclusion criteria: * 1)pregnant and lactating women; * 2)those with organ failure:heart: class iii and iv;liver: up to grade c of the child-turcotte liver -function classification;kidney: chronic kidney disease stage 4 or above; renal insufficiency stage iii or above;lungs: symptoms of severe respiratory failure with involvement of other organs;brain: central nervous system abnormalities or impaired consciousness; * 3)patients with combined second tumors; * 4)patients with active hepatitis b or c virus, hiv infection, or other untreated active infection; * 5)any severe, uncontrolled systemic autoimmune disease or any unstable systemic disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, crohn's disease, and temporal arteritis; * 6)current systemic use of steroid cell (except for recent or current use of inhaled steroids) substances; * 7) have a chronic disease requiring immunologic or hormonal therapy; * 8) have an allergy to immunotherapy and related cells; * 9) 10)patients with a history of organ transplantation or who are awaiting organ transplantation; * 10)participation in other clinical trials within the previous 30 days; * 11)those who are not suitable for clinical trials for other reasons in the opinion of the investigator.

Keywords: b7h3 car-γδt gbm