The Role of Antibody-Based Therapies in Neuro-Oncology

Abstract

This review explores the evolving landscape of antibody-based therapies in neuro-oncology, in particular, immune checkpoint inhibitors and immunomodulatory antibodies. We discuss their mechanisms of action, blood-brain barrier (BBB) penetration, and experience in neuro-oncological conditions. Evidence from recent trials indicates that while these therapies can modulate the tumor immune microenvironment, their clinical benefits remain uncertain, largely due to challenges with BBB penetration and tumor-derived immunosuppression. This review also examines emerging targets such as TIGIT and LAG3, the potential of antibodies in modulating the myeloid compartment, and tumor-specific targets for monoclonal antibody therapy. We further delve into advanced strategies such as antibody-drug conjugates and bispecific T cell engagers. Lastly, we explore innovative techniques being investigated to enhance antibody delivery, including CAR T cell therapy. Despite current limitations, these therapies hold significant therapeutic potential for neuro-oncology. Future research should focus on optimizing antibody delivery to the CNS, identifying novel biological targets, and discovering combination therapies to address the hostile tumor microenvironment.

Keywords: antibodies; brain tumor; glioblastoma; immunomodulation; immunotherapy; meningioma.

Figure 1

Illustration of Antibody Mechanisms in Neuro-oncology. (A) Overview of a centrally located brain tumor, with its vascular supply highlighted. (B) Detailed view of antibodies attempting to cross the blood-brain barrier, emphasizing the inherent challenges of this process. (C) PD-1 antibodies in action, illustrating their role in enhancing T cell functionality against tumor cells. (D) Depiction of antibody–drug conjugates (ADCs) that are attached to a cytotoxic drug, targeting and destroying tumor cells. (E) TIGIT or LAG-3 antibodies activating T cells, emphasizing their function in boosting immune response against tumor cells. (F) BiTE (Bispecific T cell Engager) mechanism, showcasing how it links T cells to tumor cells, facilitating the destruction of the tumor cells by T cells. (G) Illustration of other cells within the tumor microenvironment (TME) such as astrocytes, monocytes, and myeloid-derived suppressor cells (MDSCs). These cells can exert immunosuppressive effects, hindering effective anti-tumor immune responses. (H) Representation of lipid nanoparticles carrying antibody receptors, illustrating the potential for targeted drug delivery. (I) CAR T cell mechanism depicted as it releases BiTEs upon activation, further enhancing T cell engagement with tumor cells. (J) Detailed depiction of the anti-CTLA4 antibody mechanism: The anti-CTLA4 antibody blocks the interaction between CTLA-4 on both T regulatory and T effector cells and B7 on dendritic cells. In effector cells, CTLA-4 acts as an inhibitory receptor, reducing T cell activation. By blocking this interaction, the anti-CTLA4 antibody promotes prolonged T cell activation and increased T effector cell activity against tumor cells.