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Review
. 2017 May 15:114:19-32.
doi: 10.1016/j.addr.2017.06.006. Epub 2017 Jun 15.

Engineering challenges for brain tumor immunotherapy

Johnathan G Lyon  1 , Nassir Mokarram  2 , Tarun Saxena  2 , Sheridan L Carroll  2 , Ravi V Bellamkonda  3
Affiliations
Review

Engineering challenges for brain tumor immunotherapy

Johnathan G Lyon et al. Adv Drug Deliv Rev. .

Abstract

Malignant brain tumors represent one of the most devastating forms of cancer with abject survival rates that have not changed in the past 60years. This is partly because the brain is a critical organ, and poses unique anatomical, physiological, and immunological barriers. The unique interplay of these barriers also provides an opportunity for creative engineering solutions. Cancer immunotherapy, a means of harnessing the host immune system for anti-tumor efficacy, is becoming a standard approach for treating many cancers. However, its use in brain tumors is not widespread. This review discusses the current approaches, and hurdles to these approaches in treating brain tumors, with a focus on immunotherapies. We identify critical barriers to immunoengineering brain tumor therapies and discuss possible solutions to these challenges.

Keywords: Blood-brain barrier; Brain cancer; Glioblastoma; Immunoengineering; Immunomodulation; Immunotherapy; Lymphatics; Neuroimmunology; Neurooncoimmunology; Tumor-associated microglia.

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Figures

Figure 1
Figure 1. The Brain Tumor/Neuro-Immune Environment
(a) Brain parenchymal barriers to peripheral immune cells. The Blood-Brain Barrier (BBB), Blood-Meningeal Barrier (BMB), and the Blood-Cerebrospinal Fluid Barrier (BCSF) all actively prevent blood borne cells from entering the brain parenchyma. When a brain tumor occurs, the BBB is breached and blood-borne signals and immune cells can more readily infiltrate the brain. (b) Simplified overview of immune-suppressed cellular regulation in brain tumors.
Figure 2
Figure 2
Vaccine-based immunotherapy for brain tumors.
Figure 3
Figure 3
Adoptive Cell Therapy for brain tumors.
Figure 4
Figure 4
Monoclonal Antibody Therapy for brain tumors.
Figure 5
Figure 5
Checkpoint Inhibitor Therapy for brain tumors.
Figure 6
Figure 6
Oncolytic Virotherapy for brain tumors.
Figure 7
Figure 7
Engineering strategies to address challenges of brain cancer immunotherapies.
See this image and copyright information in PMC

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