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Published on: September 1, 2018
Prospective Molecular Targets for Natural Killer Cell Immunotherapy against Glioblastoma Multiforme
Luke C Cooksey1,2, Derek C Friesen1, Enrique D Mangan1
1Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Abstract:
Glioblastoma multiforme (GBM) is the most common type of primary malignant brain tumor and has a dismal overall survival rate. To date, no GBM therapy has yielded successful results in survival for patients beyond baseline surgical resection, radiation, and chemotherapy. Immunotherapy has taken the oncology world by storm in recent years and there has been movement from researchers to implement the immunotherapy revolution into GBM treatment. Natural killer (NK) cell-based immunotherapies are a rising candidate to treat GBM from multiple therapeutic vantage points: monoclonal antibody therapy targeting tumor-associated antigens (TAAs), immune checkpoint inhibitors, CAR-NK cell therapy, Bi-specific killer cell engagers (BiKEs), and more. NK therapies often focus on tumor antigens for targeting. Here, we reviewed some common targets analyzed in the fight for GBM immunotherapy relevant to NK cells: EGFR, HER2, CD155, and IL-13Rα2. We further propose investigating the Lectin-like Transcript 1 (LLT1) and cell surface proliferating cell nuclear antigen (csPCNA) as targets for NK cell-based immunotherapy.
Insights
Glioblastoma multiforme (GBM) immunotherapy shows promise using natural killer (NK) cells. Researchers reviewed common NK cell targets and propose Lectin-like Transcript 1 (LLT1) and cell surface proliferating cell nuclear antigen (csPCNA) as novel targets.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Therapy
Background:
- Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with poor survival rates.
- Current GBM treatments including surgery, radiation, and chemotherapy offer limited survival benefits.
- Immunotherapy is emerging as a promising strategy for various cancers, including GBM.
Purpose of the Study:
- To review current NK cell-based immunotherapy targets for GBM.
- To explore novel targets for enhancing NK cell-mediated GBM treatment.
- To highlight the potential of NK cell therapies in overcoming GBM's therapeutic resistance.
Main Methods:
- Literature review of established and potential NK cell targets in GBM.
- Analysis of tumor-associated antigens (TAAs) relevant to NK cell recognition.
- Identification of novel surface markers for NK cell targeting in GBM.
Main Results:
- Commonly investigated GBM targets for NK cell therapy include EGFR, HER2, CD155, and IL-13Rα2.
- NK cell therapies offer diverse approaches such as monoclonal antibodies, CAR-NK cells, and BiKEs.
- LLT1 and csPCNA are proposed as novel targets for NK cell-based GBM immunotherapy.
Conclusions:
- NK cell-based immunotherapies represent a significant advancement in GBM treatment strategies.
- Targeting specific antigens on GBM cells can enhance NK cell-mediated tumor killing.
- Further investigation into LLT1 and csPCNA could lead to more effective GBM immunotherapies.
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