Chapter 5 - Tumor-Specific Mutations in Gliomas and Their Implications for Immunotherapy

Abstract

Gliomas have both an inherent tendency to progress to more advanced stages and a high propensity for recurrence following standard of care therapy. Their diffusely infiltrative nature and an immunosuppressive microenvironment are contributing factors toward the therapeutic difficulties observed in patients with glioma. Advances in sequencing technology have made it possible to sequence the genome of an individual patient's tumor, shedding light on the mutation spectrum of tumors and the identification of tumor-specific antigens. These data have and will continue to have significant implications in the field of glioma immunotherapy, which seeks to harness the power of the patient's immune system to target tumor-specific mutations, offering an ideal means of treating gliomas with minimal invasiveness and off-target collateral damage. In this chapter, we identify and discuss the immunotherapeutic implications of several tumor-specific mutations, including isocitrate dehydrogenase 1-R132H, epidermal growth factor receptor vIII, and mutations in H3F3A. Additionally, the fundamental preclinical trials and the promising data from completed clinical trials will be addressed.