Advances in NK cell therapy for brain tumors

Abstract

Despite advances in treatment regimens that comprise surgery, chemotherapy, and radiation, outcome of many brain tumors remains dismal, more so when they recur. The proximity of brain tumors to delicate neural structures often precludes complete surgical resection. Toxicity and long-term side effects of systemic therapy remain a concern. Novel therapies are warranted. The field of NK cell-based cancer therapy has grown exponentially and currently constitutes a major area of immunotherapy innovation. This provides a new avenue for the treatment of cancerous lesions in the brain. In this review, we explore the mechanisms by which the brain tumor microenvironment suppresses NK cell mediated tumor control, and the methods being used to create NK cell products that subvert immune suppression. We discuss the pre-clinical studies evaluating NK cell-based immunotherapies that target several neuro-malignancies and highlight advances in molecular imaging of NK cells that allow monitoring of NK cell-based therapeutics. We review current and ongoing NK cell based clinical trials in neuro-oncology.

Unlocking Glioblastoma Secrets: Natural Killer Cell Therapy against Cancer Stem Cells

“…Collaborative research efforts involving NK cells and cytotoxic drugs like cisplatin or temozolomide have highlighted that GSCs exposed to NK cell supernatants display heightened sensitivity to these chemotherapeutic agents. These findings illuminate the potential synergy between NK cells and standard cancer treatments, offering new avenues for improving patient outcomes in the battle against highly aggressive GBM [70][71][72][73].…”

Targeting Innate Immunity in Glioma Therapy

“…NK cytotoxicity is mediated through activation signals and the downregulation of certain human leukocyte antigens (HLA) on the cell surface of target cells. A review of the preclinical and clinical use of NK cells for brain tumor therapy has been recently reported by Fares and colleagues [98]. NKs can also bind the Fc region of antibodies bound to the cell surface of tumor cells, resulting in antibody-dependent cell-mediated cytotoxicity [58].…”

“…It has since been proposed to include CAR-T cells targeting both EGFR forms. Alternatively, CAR-NKs are suitable for treating GBM as they present minimal risk of affecting normal host cells [98,100]. Still, thus far, CAR-NKs, which have shown promising results in liquid tumors, are largely unexplored in the context of GBM.…”

The peculiar challenge of bringing CAR-T cells into the brain: Perspectives in the clinical application to the treatment of pediatric central nervous system tumors

“…Despite the known low risk of toxicity compared with T cells, CAR-NK cells have some important limitations such as: short life-time, reduced cytotoxicity in vivo ( 85 ). We can hypothesize that these intrinsic characteristics would favor their use via loco-regional delivery, although some clinical evidence on the use of CAR-NK cells have shown promising results ( 86 ). An interesting advantage of NK cells relies on the possibility of deriving the product from allogeneic donors, as an “off the shelf product” ( 87 , 88 ).…”