A Head Start: CAR-T Cell Therapy for Primary Malignant Brain Tumors
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Neuro-oncology (GJ Lesser, Section Editor)
A Head Start: CAR-T Cell Therapy for Primary Malignant Brain Tumors Nicholas P. Tschernia, MD Simon Khagi, MD* Address * Division of Medical Oncology, UNC-CH, 170 Manning Drive | CB#7305, Chapel Hill, NC, 27599, USA Email: [email protected]
* Springer Science+Business Media, LLC, part of Springer Nature 2020
This article is part of the Topical Collection on Neuro-oncology Keywords CAR-T cell I Chimeric antigen receptor I Glioblastoma I GBM I Primary malignant brain tumors I Cell therapy
Opinion statement Oncology is the midst of a therapeutic renaissance. The realization of immunotherapy as an efficacious and expanding treatment option has empowered physicians and patients alike. However, despite these remarkable advances, we have only just broached the potential immunotherapy has to offer and have yet to successfully expand these novel modalities to the field of neuro-oncology. In recent years, exciting results in preclinical studies of immune adjuvants, oncolytic viruses, or cell therapy have been met with only fleeting signs of response when taken to early phase trials. Although many have speculated why these innovative approaches result in impaired outcomes, we are left emptyhanded in a field plagued by a drought of new therapies. Herein, we will review the recent advances across cellular therapy for primary malignant brain tumors, an approach that lends itself to overcoming the inherent resistance mechanisms which have impeded the success of prior treatment attempts.
Introduction Primary malignant brain tumors (PMBTs) encapsulate a spectrum of favorable and unfavorable prognosis. Within this heterogeneous group, we find the malignancy, glioblastoma (GBM), which unfortunately carries the highest incidence (4.40 per
100,000) and prevalence (9.23 per 100,000) of PMBTs; worse still, it is the subtype that holds the lowest 5- and 10-year survival rates (5.4% and 2.7%, respectively) [1]. Despite stepwise advances in treatment across surgery, radiotherapy, and
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chemotherapy, the median survival remains slightly over a year at 12–15 months [2, 3].
Immunotherapeutic renaissance In the preceding decade, we have seen a revolution in oncology that harkens back to the foundations of immunotherapy championed by William B. Coley in the 1890s, when he injected inoperable tumors with cultures of erysipelas [4]. Over a century later, this revolution has been met with tremendous success following the expansion of checkpoint inhibitors across hematologic and solid malignancies [5, 6], yet these practicechanging outcomes have not translated into the realm of the neuro-oncologist. At this time, there are no FDAapproved immunotherapies for PMBTs despite many unique therapies currently in clinical trials [7]. Over the last 20 years, we have learned that PMBTs, and GBM in particular, are highly immunosuppressive tumors [7–10] and there are limitations to a safe immune response in the central nervous system [11]. To date, we have learned a substantial amount through
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