Plant Virus-Like Particle In Situ Vaccine for Intracranial Glioma Immunotherapy.

Steinmetz Steinmetz,Shukla Shukla,Beiss Beiss,Sloan Sloan,Harris Harris,Kerstetter-Fogle Kerstetter-Fogle,Wang Wang

doi:10.3390/cancers11040515

Abstract

Despite aggressive multi-modality treatment with surgery, radiation and chemotherapies, malignant glioma inevitably recurs and has dismal survival rates. Recent progress in immunotherapy has led to a resurgence of interest, and immunotherapies are being investigated for treatment of glioma. However, the unique brain anatomy and a highly immunosuppressive glioma microenvironment pose significant challenges to achieving efficacy. Thus, there is a critical need for assessment of next-generation immunotherapies for glioma. In this study, we have investigated the efficacy of the nanoparticle platform technology based on plant-derived Cowpea mosaic virus like particles (empty CPMV or eCPMV) to instigate a potent immune response against intracranial glioma. CPMV immunotherapy has been shown to efficiently reverse the immunosuppressive tumor microenvironments in pre-clinical murine models of dermal melanoma and metastatic melanoma, metastatic breast cancer, intraperitoneal ovarian cancer and in canine patients with oral melanoma. In the present study, we demonstrate that in situ administration of CPMV immunotherapy in the setting of glioma can effectively recruit unique subset of effector innate and adaptive immune cells to the brain parenchyma while reducing immune suppressive cellular population, leading to regression of intracranial glioma. The in situ CPMV nanoparticle vaccine offers a potent yet safe and localized immunotherapy for intracranial glioma.

Highlights

Malignant glioma represents one of the most aggressive forms of cancer, with poor survival rates that have not changed in the past three decades despite advancements in detection and treatment modalities
Unmodified empty CPMV (eCPMV) is represented by two distinct bands corresponding to the ~24 kDa small coat protein (S-CP) subunit and the ~42 kDa large coat protein subunit (L-CP)
Our results illustrate that eCPMV-mediated modulation of the immunological landscape in the brain tumor microenvironment (TME) supports anti-tumor response in our murine model

Summary

Introduction

Malignant glioma represents one of the most aggressive forms of cancer, with poor survival rates that have not changed in the past three decades despite advancements in detection and treatment modalities. Even with aggressive treatments including debulking, chemotherapy and radiation the median survival rates for malignant glioma is 12 months, with a five-year relative survival of about. Glioma is associated with high rates of morbidity due to damage to functional regions of the brain. Radiation and chemotherapy are the mainstay of treatment regimens [3]. The blood brain barrier (BBB) limits the penetration and clinical efficacy of most systemic chemotherapies [4]. Residual tumor subpopulations resistant to radio- and chemotherapy eventually lead to recurrence and treatment failure [5,6]

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Discussion

Conclusion