Diffuse Intrinsic Pontine Glioma or Glioblastoma Clinical Trial
Official title:
Immune Modulatory DC Vaccine Against Diffuse Intrinsic Pontine Glioma (DIPG) and Glioblastoma (GBM)
This study is designed to treat patients who have been diagnosed with brain cancer, including glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). The treatment uses immunomodulatory vaccine generated by autologous dendritic cells (DCs) pulsed with genetically modified tumor cells or tumor-related antigens including neoantigens to inject into patients. Vaccine-induced T cell responses have been associated with improved survival. The study will evaluate the safety and potential benefit of the novel immunomodulatory DC vaccines.
Diffuse intrinsic pontine glioma (DIPG) or glioblastoma (GBM) is an aggressive malignancy.
DIPG mainly occurs in the ventral pontine of childhood. The overall median survival time is 9
to 11 months. The 2-year survival rate is less than 10%. Thus DIPG has become one of the most
fatal diseases in children. These tumors invade and infiltrate the surrounding brain, making
complete surgical excision impossible. Several studies focused on the identification of GBM
or DIPG-specific antigens and evaluated their potential for vaccine application.
Immunomodulatory DC vaccines based on ex vivo genetic modifications in combination with known
tumor-specific antigens may substantially enhance the activation potential of tumor-specific
T cells with improved benefit to patients.
Although certain antigens are highly specific in DIPG or GBM, existing immune tolerance
suppresses anti-tumor immunity in cancer patients. To induce anti-cancer immune response in
patients, ex vivo modification of immune modulatory antigens or immune cells will be
necessary. Advanced whole exome sequencing has been developed to identify specific mutations
in tumors and predict best-fit MHC-specific neoepitopes for T cell activation. In this study
we will investigate novel DC vaccines based on autologous DCs pulsed with genetically
modified tumor cells or related antigens such as neoantigens to induce a strong anti-tumor
immunity. Early studies of DC-based vaccines targeting gliomas have shown acceptable safety
and low toxicity profile. This is a multi-center randomized Phase I study to evaluate safety
of novel DC vaccines.
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