Inclusion Criteria:
1. Diagnosed with glioblastoma through histopathological examination;
2. Patients with unresectable recurrent or progressive glioblastoma who have failed or
are intolerant to standard treatment; 8.1The standardized systematic treatment
received by patients must comply with the 2022 edition of the "Guidelines for the
Treatment of Gliomas"; 8.2Requirements for treating intolerance: Refers to patients
who are unable to continue the current effective systemic standardized treatment due
to toxic side effects such as vomiting, diarrhea, abdominal pain, bone marrow
suppression, etc. of grade ≥ 3. Refusal due to economic or personal reasons is not
accepted;
3. Age ≥ 18 years old, including boundary values;
4. Expected survival period greater than 2 months;
5. There is at least one measurable intracranial lesion that meets the criteria of
Neuro Tumor Response Evaluation (RANO);
6. Patients must provide tumor samples within 2 years that meet the requirements
(paraffin blocks or unstained sections with a quantity that meets the testing
requirements specified in this study) and have positive CD276 expression detected by
immunohistochemistry;
7. Karnofsky (KPS) functional status score ≥ 60 points;
8. Blood routine:
8.1Hemoglobin (Hb) ≥ 90g/L; 8.2Absolute neutrophil count (ANC) ≥ 1.5 × 10 ^ 9/L;
8.3Platelet count (PLT) ≥ 70 × 10 ^ 9/L; 8.4Absolute value of lymphocytes ≥ 0.5 × 10
^ 9/L;
9. The liver, kidney, heart, and lung functions meet the following requirements:
9.1Creatinine clearance rate ≥ 60ml/min; 9.2Alanine transaminase (ALT) and aspartate
transaminase 9.3Aspartate aminotransferase (AST) ≤ 2.5 × ULN, total bilirubin (TBL)
≤ 1.5 × ULN (for the elevation of ALT and AST that can be explained by liver
invasion, AST and ALT high limit can be upregulated up to 5-fold, and TBL high limit
can be upregulated up to 3-fold); 9.4Serum albumin ≥ 3.0g/dL; 9.5Left ventricular
ejection fraction ≥ 50%, no pericardial effusion [ECHO (Echocardiography, ECHO)
examination], no clinically significant ECG (Electrocardiogram, ECG) results;
9.6Blood oxygen saturation is greater than 95% under non oxygen inhalation
conditions.
10. Women of childbearing age who have a negative blood pregnancy test before the start
of the trial and agree to take effective contraceptive measures during the trial
period until the last follow-up; Male participants with reproductive partners agree
to take effective contraceptive measures during the trial period until the last
follow-up;
11. Those who voluntarily participate in this experiment and sign the informed consent
form.
Exclusion Criteria:
1. Those who require the use of immunosuppressants; Or individuals with autoimmune
diseases;
2. Patients who have received or are waiting for organ transplantation in the past;
3. The toxicity caused by previous treatment has not stabilized or recovered to ≤ level
1 (except for cases judged by the researcher to be clinically insignificant);
4. There is a large amount of uncontrollable serosal fluid accumulation (such as
pleural effusion, abdominal effusion, pericardial effusion) after treatment;
5. Use any of the following drugs or treatment methods within the specified time before
cell collection:
5.1Used therapeutic doses of corticosteroids within one week prior to cell
collection. But the use of topical and inhaled steroids is allowed; 5.2Received
chemotherapy drugs within one week prior to cell collection. If the oral
chemotherapy drug has passed at least 3 half lives before cell collection, it is
allowed to be included in the group; 5.3Individuals who use drugs to stimulate bone
marrow hematopoietic cell production within 5 days prior to cell collection;
6. CNS diseases that have clinical significance in the past or screening, and have been
assessed by researchers as having safety risks;
7. Individuals who have previously used any gene therapy products;
8. Active hepatitis B or hepatitis C virus is defined as: subjects who are positive for
hepatitis B B virus surface antigen (HBsAg) or hepatitis B B core antibody (HBcAb)
and whose peripheral blood HBV DNA titer is higher than the upper limit of
detection; Individuals with positive hepatitis C virus (HCV) antibodies and positive
peripheral blood HCV RNA (HCV RNA); People infected with AIDS virus and syphilis;
9. Active EBV and cytomegalovirus are defined as patients with positive or negative IgM
antibodies in EBV serum but EBV-DNA levels higher than normal; Patients with IgM
antibody positive or IgM antibody negative but CMV-DNA higher than normal in the
serum of cytomegalovirus (CMV);
10. Used the research drug within 4 weeks prior to cell collection. But if the
experimental treatment is ineffective or if the disease progresses, and at least 5
half lives have passed before cell collection, it is allowed to be included in the
group;
11. Received radiation therapy within 4 weeks prior to cell collection;
12. Patients who have undergone major surgical procedures or significant trauma within 4
weeks prior to cell collection, or who are expected to undergo major surgery during
the study period;
13. If immunotherapy such as anti-PD1 and PD-L1 has been used before cell infusion, at
least 5 half lives must be passed between the last dose and CAR-T cell infusion;
14. Abnormal cardiac function includes: long QTc syndrome or QTc interval>480 ms;
Complete left bundle branch block, grade II/III atrioventricular block; Severe and
uncontrolled arrhythmias requiring medication treatment; History of chronic
congestive heart failure and NYHA ≥ 3 (refer to Appendix 4) with a heart ejection
fraction below 50% within the 6 months prior to screening; Heart valve disease with
CTCAE ≥ 3 grade; Within the first 6 months of screening, there has been a history of
myocardial infarction, cardiac angioplasty or stent implantation, unstable angina,
severe pericardial disease, or other clinically significant heart diseases;
15. Patients who require anticoagulant therapy;
16. Patients requiring long-term antiplatelet therapy;
17. Start screening for symptomatic history of venous thrombosis or pulmonary embolism
within the previous 6 months;
18. History of malignant tumors other than non melanoma skin cancer or carcinoma in situ
(such as cervical, bladder, breast) (unless in a disease-free state for at least 3
years);
19. Infections (fungal, bacterial, viral, or other) that require intravenous injection
of antibiotics for control or are uncontrollable, such as simple urinary tract
infections and bacterial pharyngitis, can be included if the researcher evaluates
that they can be controlled through treatment;
20. Unable to perform MRI examination (such as installing pacemakers, metal dentures,
etc.)
21. The researcher shall determine whether the patient has any factors that affect
compliance with the protocol, or is unwilling or unable to comply with the
procedures required in the research protocol.
