Antibody, T-cell and Dendritic Cell Immunotherapy for Malignant Brain Tumors

Abstract

Modest improvement in brain tumor patient survival has been achieved through advances in surgical, adjuvant radiation and chemotherapeutic strategies. However, these traditional approaches have been unsuccessful in permanently controlling these aggressive tumors, with recurrence being quite common. Hence, there is a need for novel therapeutic approaches that specifically target the molecularly diverse brain tumor cell population. The ability of the immune system to recognize altered tumor cells while avoiding surrounding normal cells offers an enormous advantage over the nonspecific nature of the conventional treatment schemes. Therefore, immunotherapy represents a promising approach that may supplement the standard therapies in eliminating the residual brain tumor cells. This review summarizes different immunotherapeutic approaches currently being tested for malignant brain tumor treatment.

A concise review of immunotherapy for glioblastoma

“…The use of monoclonal antibodies as a passive immunotherapy approach may result in killing of tumor cells through different mechanisms [27] . Sparing of normal brain tissue without tumor may be achieved if the antigen targeted by the monoclonal antibody is specifically expressed by the tumor only.…”

Chimeric antigen receptor engineered T cells can eliminate brain tumors and initiate long-term protection against recurrence

“…EGFRvIIIC CAR targeted destruction of GBM [1] results in release of immunostimulatory cytokines by T cells and antigens and DAMPs by dying tumor cells [2]. APCs are recruited to the site of tumor destruction where they engulf dying tumor cells and become activated by DAMPs [3].…”

“…1 The current standard of care includes tumor resection, radiation, and chemotherapy. This conventional treatment is inherently nonspecific and is profoundly detrimental to patient quality of life.…”

“…1,5 We recently developed murine and human third-generation (CD3z. CD28.4-1BB) CARs targeting the EGFRvIII mutation (EGFRvIII C CARs) to evaluate their ability to traffic to the brain, localize to invasive tumor deposits, and treat intracranial (IC) gliomas.…”

Ex vivo generation of dendritic cells from cryopreserved, post-induction chemotherapy, mobilized leukapheresis from pediatric patients with medulloblastoma

“…The development of effective therapies that are specific and not associated with additional toxicity is critical in improving clinical outcomes for children affected by malignant brain tumors. Immunotherapy is a promising treatment strategy that could meet this clear and urgent need [8–11]. …”