4SCAR-IgT Against Glioblastoma Multiform


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Primary Outcome Measures:
Secondary Outcome Measures:

  • Treatment Responses recurrent glioblastoma [ Time Frame: 4 weeks ]

    defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).

  • Overall Survival Rate [ Time Frame: 2 years ]

    Percentage of Participants With Objective Response as Determined by the Investigator With Use of Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)

  • Progression-free Survival Rate [ Time Frame: 2 years ]

    Progression-free Survival (PFS) as Determined by the Investigator With Use of RECIST v1.1

  • Persistence and proliferation of CAR T cells in patients [ Time Frame: 2 years ]

    CAR-T cell percentage in the peripheral blood by flow or qPCR

  • production of specific immune check point antibodies [ Time Frame: 2 years ]

    specific antibody in peripheral blood will be measured by ELISA

Background:

Glioblastoma multiforme (GBM) is the most dangerous and aggressive form of brain cancer. Chimeric antigen receptor (CAR)-modified T cells can mediate long-term durable remissions in recurrent or refractory CD19+ B cell malignancies, and are a promising therapy to treat GBM. Epidermal growth factor receptor variant III, EGFRvIII is one of the GBM tumor antigens expressed in about 30% of glioblastomas. EGFRviii is a mutated form of EGFR protein, a neo-antigen, and is not expressed in normal tissues.

Tumor microenvironment has been known to inhibit immune responses. Many immune checkpoint inhibitors are now being tested for targeting various cancers. Instead of infusing antibody, we plan to infuse antibody-producing T cells (IgT) based on tumor surface antigen guided CAR-Tcells. EGFRvIII is an attractive target for GBM CAR-T therapy. Combination of EGFRviii or other GBM-specific CAR-T and IgT strategy, the CAR-IgT cells could target both the tumor cells and the tumor microenvironment.