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Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
Genetically Modified Cellular Therapies for Malignant Gliomas
Michael Kilian1, Theresa Bunse1,2, Wolfgang Wick3,4
1DKTK (German Cancer Consortium), Clinical Cooperation Unit (CCU), Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Abstract:
Despite extensive preclinical research on immunotherapeutic approaches, malignant glioma remains a devastating disease of the central nervous system for which standard of care treatment is still confined to resection and radiochemotherapy. For peripheral solid tumors, immune checkpoint inhibition has shown substantial clinical benefit, while promising preclinical results have yet failed to translate into clinical efficacy for brain tumor patients. With the advent of high-throughput sequencing technologies, tumor antigens and corresponding T cell receptors (TCR) and antibodies have been identified, leading to the development of chimeric antigen receptors (CAR), which are comprised of an extracellular antibody part and an intracellular T cell receptor signaling part, to genetically engineer T cells for antigen recognition. Due to efficacy in other tumor entities, a plethora of CARs has been designed and tested for glioma, with promising signs of biological activity. In this review, we describe glioma antigens that have been targeted using CAR T cells preclinically and clinically, review their drawbacks and benefits, and illustrate how the emerging field of transgenic TCR therapy can be used as a potent alternative for cell therapy of glioma overcoming antigenic limitations.
Insights
Chimeric antigen receptor (CAR) T cell therapy shows promise for brain tumors, but faces challenges. Transgenic T cell receptor (TCR) therapy offers a potential alternative for treating malignant glioma.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Cancer Genetics
Background:
- Malignant glioma remains a significant challenge with limited treatment options beyond surgery and radiochemotherapy.
- While immune checkpoint inhibition benefits peripheral tumors, its efficacy in brain tumors is limited.
- Advances in sequencing identified tumor antigens, leading to CAR T cell therapy development.
Purpose of the Study:
- To review glioma antigens targeted by CAR T cells in preclinical and clinical settings.
- To discuss the benefits and drawbacks of current CAR T cell approaches for glioma.
- To explore transgenic T cell receptor (TCR) therapy as an alternative for glioma treatment.
Main Methods:
- Literature review of preclinical and clinical studies on CAR T cell therapy for glioma.
- Analysis of identified glioma antigens and their targeting strategies.
- Evaluation of transgenic TCR therapy as a potential cell therapy for glioma.
Main Results:
- Numerous CARs have been designed and tested for glioma, showing biological activity.
- CAR T cell therapy for glioma faces challenges, including antigen limitations and clinical efficacy.
- Transgenic TCR therapy presents a promising alternative to overcome antigenic limitations.
Conclusions:
- CAR T cell therapy holds potential for malignant glioma but requires further optimization.
- Transgenic TCR therapy offers a novel approach to enhance cell therapy efficacy in glioma.
- Future research should focus on overcoming current limitations in brain tumor immunotherapy.
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