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Immunotherapy Approaches to Glioma

While our understanding of the biological basis of brain tumor development has improved and newer treatment modalities have been developed, survival for many types of malignant primary brain tumors has not improved significantly. Malignant glioma is the most common and aggressive primary brain cancer in adults. It is a deadly disease and remains so despite many novel therapies. Some of these therapies are in the clinic, while others are currently in different stages of clinical testing. It is important to bring to the clinic newer treatments that can improve the survival and quality of life of patients with gliomas. At CureScience™ Institute, we are focused on developing more effective therapies against glioma.
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Malignant gliomas can suppress the immune system and prevent cells of the immune system from attacking the tumor in the body. Suppression of the body’s natural immune response leads to aggressive and unchecked tumor growth.  To improve the survival of patients with these tumors, it is important to allow the body’s immune system to mount a strong response against gliomas.  This novel approach, coupled with the newer drugs (alone, in combination, and in multiple therapies) that kill the tumor cells, may improve patient survival. Currently, there is no immunotherapy for malignant gliomas that is approved by the U.S. Food and Drug Administration (US FDA). However, cancer peptide vaccines are a promising cancer immunotherapy that can induce cancer-specific cytotoxic T lymphocytes (CTLs) in tumors. The peptides are designed based on tumor biomarkers or mutations to bind to major histocompatibility complex (MHC) classes I and MHC class II. The promising results from two of the most recent phase I clinical trials show that personalized peptide vaccination to newly diagnosed glioblastoma patients generates tumor-reactive T cells, which can infiltrate glioblastomas and make tumor cells potentially susceptible to further immunotherapy approaches. The development of a universal neoantigen vaccine for one or more common types of human leukocyte antigen (HLA) phenotype could potentially treat a number of patients with more malignant gliomas.

In addition, just as each individual has a unique immunogenic profile, each tumor is unique in its immunogenicity. Thus, another approach we are considering is to tailor an immunotherapeutic that is specific not only for an individual but also for the tumor. Using computational methods in the identification and validation of biomarkers using DNA, RNA, and protein sequences aids in the excavation of key genes involved in the development of cancer. Tumor antigens expressed solely on tumor cells, unique to an individual’s own tumor, can be screened with these predictive algorithms to make a personalized vaccine. To this end, we are working in collaboration to test a vaccine against neoantigen peptides that are present in tumors but not normal tissue. By measuring immune diagnostics at the single cell level, we can reliably identify biological functions. In combination with other targeted therapies and immunotherapeutic agents, vaccines of this type hold promise in mitigating cancer.

Written By: Feng Lin, M.D., Ph.D.
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