Safety and Efficacy Study of TX103 CAR-T Cell Therapy for Recurrent or Progressive Grade 4 Glioma.

Inclusion Criteria:

1. Subjects must voluntarily participate in the study and sign a written informedconsent document; subjects should be willing and able to follow and complete studyprocedures.

2. Male or female subjects aged 18 to 75 years (both inclusive).

3. Subject must have histologically diagnosed grade 4 glioma, such as glioblastoma,grade 4 astrocytoma, diffuse hemispheric glioma, according to 2021 WHOClassification of Tumors of the CNS. Subjects must have had experienced diseaserecurrence or progression* after surgery combined with Stupp regimen (concurrentradiotherapy and temozolomide (TMZ) followed by adjuvant TMZ) and are not candidatefor re-resection. For subjects harboring specific gene mutations, such as NTRK genefusion or BRAF V600E mutation, they must have also progressed on correspondingmutation-directed therapies before enrollment.

• Disease recurrence or progression must be confirmed by radiographic orhistopathological diagnosis.

4. Subjects with confirmed B7-H3 positive* (≥30%) tumor expression byimmunohistochemistry (IHC) in either primary or recurrent tumor tissue.

*B7-H3 positive rate is defined as the percentage of B7-H3 positive tumor cells innon-necrotic tumor tissue.

5. Subjects with KPS score of ≥60.

6. Subjects should have adequate venous access for collection of peripheral bloodmononuclear cells (PBMCs).

7. Subjects with left ventricular ejection fraction (LVEF) ≥ 40% within one month priorto the first dose.

8. Subjects with oxygen saturation ≥95% under the resting state.

9. Subjects with adequate organ function, as indicated by laboratory test results thatmeet the following criteria:

• Hematological function: Absolute neutrophil count (ANC) ≥1.5×109/L, hemoglobin (Hb) ≥90g/L, platelet count (PLT) ≥100×109/L, absolute lymphocytes count (ALC) ≥0.15×109/L. Blood transfusion, granulocyte (macrophage) colony stimulatingfactor, recombinant human erythropoietin, recombinant human thrombopoietin,platelet receptor agonist, recombinant human interleukin-11, and othersupportive treatments are prohibited within 14 days before the test.

• Liver function: Total bilirubin (TBIL) ≤ 1.5 × ULN, patients with Gilbert'ssyndrome (persistent or recurrent hyperbilirubinemia, presenting asunconjugated bilirubin in the absence of evidence of hemolysis or liverpathology) Except for elevated erythrocytes; alanine aminotransferases (ALT)and aspartate aminotransferase (AST) ≤2.5×ULN.

• Renal function: serum creatinine (Scr) ≤1.5×ULN.

• Coagulation function (in the absence of anticoagulant therapy): prothrombintime (PT) or activated partial thromboplastin time (APTT) or internationalnormalized ratio (INR) ≤ 1.5×ULN.

• Female subjects of childbearing potential must have a negative serum pregnancytest at screening and if a positive urine test or a negative result cannot beconfirmed by urine test.

10. Women of childbearing potential (which refer to women who have not been surgicallysterilized and pre-menopausal women) should use highly effective and reliable methodof contraception (refer to Section 5.3 for contraception method) from the start ofthe study until 6 months after the last dose of the study drug; sexually active malesubjects, if no vas deferens for ligation, consent must be given to the use ofhighly effective and reliable method of contraception from the start of the studyuntil 6 months after the last dose of the study drug.

Exclusion Criteria:

1. Pregnant or breastfeeding female subjects.

2. Subjects with viral infection during the screening period:

• Serum HIV antibody positive, treponema pallidum serology positive; OR

• Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV DNA testvalue exceeds the normal range; OR

• Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNApositive.

3. Medical history and concomitant diseases:

• Subjects who have received carmustine extended-release implantation surgerywithin 6 months;

• Subjects with known or suspected active autoimmune diseases, including but notlimited to Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus,etc.;

• Subjects who are receiving systemic immunosuppressive agents or subjects whoneed to use immunosuppressive agents for a long-time during treatment, exceptfor intermittent topical, inhaled, or intranasal glucocorticoid therapy;

• Subjects with uncontrolled mental disorders, or who, in the Investigator'sopinion, have a medical history or a history of mental states that may increasethe risks associated with study participation or study drug administration, orthat may interfere with the results;

• The toxicity and side effects caused by previous treatment have not recoveredto ≤ grade 1 (per CTCAE 5.0); except for alopecia and other tolerable eventsjudged by the Investigator;

• Subjects who have participated in other interventional clinical studies withinthe past 1 month;

• Subjects who have previously received CAR-T cell therapy or other genetherapy*;

• Subjects with any serious or poorly controlled disease that, in the opinion ofthe Investigator, may increase the risk associated with study participation,study drug administration, or affect the subject's ability to receive studydrug, including but not limited to cardiovascular and cerebrovascular diseases,renal insufficiency, pulmonary embolism, coagulopathy or requiring long-termanticoagulant therapy, active infection or uncontrollable infection requiringlong-term systemic treatment;

• Subjects with other malignant tumors in the past 3 years or at present, exceptfor non-melanoma skin cancer, carcinoma in situ (such as cervix, bladder andbreast cancer).