Cellular Immunotherapy for High-Grade Glioma
Cellular Immunotherapy for High-Grade Glioma
The outcome for patients with the most common primary brain tumor, glioblastoma multiforme (GBM), remains poor. Several immunotherapeutic approaches are actively being pursued including antibodies and cell-based therapies. While the blood–brain barrier protects brain tumor cells from therapeutic antibodies, immune cells have the ability to traverse the blood–brain barrier and migrate into GBM tumors to exert their therapeutic function. Results of Phase I clinical studies with vaccines to induce GBM-specific T cells are encouraging and Phase II clinical trials are in progress. Nonvaccine-based cell therapy for GBM has been actively explored over the last four decades. Here we will review past clinical experience with adoptive cell therapies for GBM and summarize current strategies on how to improve these approaches.
Primary brain tumors continue to pose significant clinical challenges. Tumors derived from astrocytes are the most common and among them glioblastoma multiforme (GBM) is the most aggressive. Despite advances in surgical procedures, radiation therapy and chemotherapy, the outcome for GBM is only slowly improving and 5-year overall survival rates remain low. Thus, new targeted therapies are needed to improve current treatment strategies. Among them, immunotherapy is an attractive approach since it does not rely on the cytotoxic pathways of conventional therapies. Cellular immunotherapies for GBM, which are nonvaccine based, have been explored for the last four decades (Table 1). In this article, we will review these approaches and summarize potential strategies on how to improve them. Vaccine-based approaches have been recently reviewed elsewhere.
Abstract and Introduction
Abstract
The outcome for patients with the most common primary brain tumor, glioblastoma multiforme (GBM), remains poor. Several immunotherapeutic approaches are actively being pursued including antibodies and cell-based therapies. While the blood–brain barrier protects brain tumor cells from therapeutic antibodies, immune cells have the ability to traverse the blood–brain barrier and migrate into GBM tumors to exert their therapeutic function. Results of Phase I clinical studies with vaccines to induce GBM-specific T cells are encouraging and Phase II clinical trials are in progress. Nonvaccine-based cell therapy for GBM has been actively explored over the last four decades. Here we will review past clinical experience with adoptive cell therapies for GBM and summarize current strategies on how to improve these approaches.
Introduction
Primary brain tumors continue to pose significant clinical challenges. Tumors derived from astrocytes are the most common and among them glioblastoma multiforme (GBM) is the most aggressive. Despite advances in surgical procedures, radiation therapy and chemotherapy, the outcome for GBM is only slowly improving and 5-year overall survival rates remain low. Thus, new targeted therapies are needed to improve current treatment strategies. Among them, immunotherapy is an attractive approach since it does not rely on the cytotoxic pathways of conventional therapies. Cellular immunotherapies for GBM, which are nonvaccine based, have been explored for the last four decades (Table 1). In this article, we will review these approaches and summarize potential strategies on how to improve them. Vaccine-based approaches have been recently reviewed elsewhere.