Suitable for the surgery of the placement of the Ommaya catheter.Relapsed/refractory disease confirmed by radiographic evidence after standard therapy.Clinical Pathology confirms B7-H3 positive tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score >= 50).Histologically confirmed diagnosis of World Health Organization (WHO) classification grade IV glioblastoma (GBM).Documented informed consent of the participant and/or legally authorized representative.Control group: Patients will receive regular cycles of Temozolomide treatment with 5 days of treatment and 23 days of interval.Patients may receive additional CAR-T cycles at the discretion of the principal investigator and oncologist. Temozolomide treatment during the cycles of CAR-T injections will be stopped and resumed next cycle. The CAR-T injections occur in between Temozolomide (TMZ) cycles. 3 injections of CAR-T are planned at two different doses with 1-2 weeks intervals. CAR-T cells are expanded ex vivo and infused back to patients via intratumoral or intracerebroventricular injection through an Ommaya catheter.
Experimental group: Patients autologous T cells are activated and transduced with retrovirus containing B7-H3 CAR.To access the pharmacokinetics and pharmacodynamics of B7-H3 CAR-T in between Temozolomide cycles.To compare the overall survival (OS) and progression-free survival (PFS) of R/R GBM patients treated with B7-H3 CAR-T in between Temozolomide cycles vs Temozolomide alone.To evaluate the safety and tolerability intratumoral/intracerebroventricular injection of B7-H3 CAR-T when used in between Temozolomide cycles.The investigators constructed a retroviral vector encoding a chimeric antigen receptor (CAR) targeting B7-H3, which can mediate CAR transfer into patient T cells with high efficiency.Therefore, it is an attractive GBM target for CAR-T therapy B7-H3 is not expressed in normal tissues especially not in central nervous system.B7-H3 is expressed in 70% of patients with glioblastoma.Why Should I Register and Submit Results?.
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