Inclusion Criteria:
- - 1) Agree to follow the study treatment plan and visit plan, voluntarily enroll, and
sign the informed consent in writing; 2) Aged ≥18 years old on the day of signing
the informed consent, regardless of gender; 3) Patients with recurrent/refractory
glioma who have failed or cannot tolerate standard treatment and whose CD70
expression is confirmed by cytology or histology; 4) According to the results of
immunohistochemistry test in a tertiary hospital (if historical tissue samples show
CD70 positivity, no retest is required; if historical tissue samples show CD70
negative, a puncture biopsy is required) [historical archived tissue samples within
2 years are acceptable], the CD70 expression in the tumor site of the subject meets
the positive standard, that is, ≥2+; 5) According to the RANO standard (Appendix 1),
there is at least one evaluable or measurable lesion; 6) The expected survival
period is ≥12 weeks; 7) The baseline Kanofsky performance score (Kanofsky
performance score, KPS) score ≥ 70 points; 8) Subjects have adequate organ and bone
marrow function and meet the following laboratory test standards: Bone marrow
function: absolute neutrophil count (ANC) ≥ 1.5×109/L (1500/mm3); platelets (PLT) ≥
90×109/L (1×105/mm3) (no blood transfusion or use of auxiliary white blood cells and
platelets within 14 days before screening); White blood cell count ≥ 3.0×109/L
(3000/mm3); Hemoglobin (HGB) ≥ 9.0 g/dL; Liver function: serum bilirubin (T-Bil) ≤
1.5 times the upper limit of normal (ULN), Gilbert's syndrome (Gilbert's syndrome)
(persistent or recurrent hyperbilirubinemia, manifested as elevated unconjugated
bilirubin in the absence of evidence of hemolysis or liver pathology); patients
without liver metastasis, aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) ≤ 3 times ULN, patients with liver metastasis, ALT and AST ≤
5 times ULN; Renal function: serum creatinine ≤ 1.5 times ULN, or creatinine
clearance (Ccr) ≥ 50 mL/min (Ccr is calculated using the Cockcroft-Gault formula,
see Appendix 5); Coagulation function: international normalized ratio (INR) ≤ 1.5
times ULN, activated partial thromboplastin time (APTT) ≤ 1.5 times ULN; 9) The
investigator judges that the patient must have fully recovered from the previous
treatment toxicity to ≤ Grade 1, except for the following situations: a.
Alopecia;
b. Pigmentation; c. Late toxicity caused by radiotherapy, which cannot be recovered
by the investigator; d. Neurotoxicity of Grade 2 or below caused by platinum (CTCAE
5.0); Fertility-bearing male and female subjects of childbearing age must use
effective contraceptive methods from the time they sign the informed consent until
at least 6 months after CAR-T administration, and until 2 consecutive PCR tests show
that there are no more CAR-T cells in the body. Women of childbearing age include
premenopausal women and women within 2 years after menopause. Women of childbearing
age must have a negative pregnancy test result within 7 days before the first dose.
Exclusion Criteria:
- - 1) Patients who have received any treatment related to the CD70 target within 3
years; 2) Patients who have received any experimental drug treatment or used
experimental devices within 28 days before CAR-T administration; 3) Patients who
have received any systemic anti-tumor treatment within 28 days or 5 half-lives
(whichever is longer) before CAR-T administration, including systemic chemotherapy,
immunotherapy, hormone therapy (excluding glucocorticoids), targeted therapy,
systemic immunomodulators (including but not limited to interferon, interleukin 2
and tumor necrosis factor), and received Chinese herbal medicine or Chinese patent
medicine with anti-tumor effects within 14 days before CAR-T administration; 4)
Patients who have received radiotherapy within three months before administration;
5) Patients who have received other non-CD70 target cell therapy products within two
months before administration; 6) Patients who have received other cell therapy
products in the past need to undergo RCL testing during the screening period, and
patients with positive results in any test; 7) Patients who have received
therapeutic doses of glucocorticoids within 14 days before CAR-T administration
(however, physiological replacement doses of glucocorticoids are allowed, such as 10
mg/day prednisone or equivalent); 8) Patients who received oral or intravenous
anticoagulation within 7 days before CAR-T cell administration; 9) Patients with
other malignant tumors previously or concurrently, with the following exceptions:
Carcinoma in situ that has been cured and has no signs of recurrence for at least 3
years before the study; The primary malignant tumor has been completely resected and
in complete remission for ≥5 years.
10) History of allogeneic organ transplantation
or allogeneic hematopoietic stem cell transplantation; 11) Those with
immunodeficiency or autoimmune diseases, or those who need to use
immunosuppressants; 12) Those who have received live vaccine immunization within 14
days before screening, or those who need to receive live vaccine immunization during
the study; 13) Severe or uncontrollable systemic disease or any unstable systemic
disease, including but not limited to uncontrolled hypertension, uncontrolled
hyperglycemia, hepatic and renal dysfunction or metabolic diseases, central nervous
system diseases, etc.; 14) Known severe cardiovascular disease, congenital long QT
syndrome, torsades de pointes, myocardial infarction in the past 6 months, or
arterial thrombosis, or unstable angina, or congestive heart failure of grade 3 or
above (including grade 3) according to the New York Heart Association (NYHA)
classification (see Appendix 3), or left ventricular ejection fraction (LVEF) <50%,
QTc interval >450 ms for men and >470 ms for women ms; 15) Any one or both of the
test results of Treponema pallidum antibody or human immunodeficiency virus (HIV)
antibody are positive, cytomegalovirus (CMV) antibody IgM test is positive and CMV
DNA titer is more than 2 times higher than the upper limit of normal value;
Epstein-Barr virus antibody IgM test is positive and EBV DNA titer is more than 2
times higher than the upper limit of normal value; Hepatitis C virus antibody is
positive and hepatitis C virus (HCV) RNA titer is more than 2 times higher than the
upper limit of normal value, or active hepatitis B patients (defined as HBsAg
positive and peripheral blood HBV DNA titer is more than 2 times higher than the
upper limit of normal value); 16) Pregnant or lactating women; The researchers
believe that the subjects have other conditions that may affect compliance or are
not suitable for participating in this study.
