Inclusion Criteria:
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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.
