Contemporary RNA Therapeutics for Glioblastoma

Kaitlyn Melnick, Farhad Dastmalchi, Duane Mitchell, Maryam Rahman, Elias J Sayour, Kaitlyn Melnick, Farhad Dastmalchi, Duane Mitchell, Maryam Rahman, Elias J Sayour

Abstract

Glioblastoma (GBM) is the most common primary brain tumor in adults and is universally lethal with a median survival of less than two years with standard therapy. RNA-based immunotherapies have significant potential to establish a durable treatment response for malignant brain tumors including GBM. RNA offers clear advantages over antigen-focused approaches but cannot often be directly administered due to biological instability. This review will focus on utilization of RNA dendritic cell vaccines and RNA nanoparticle therapies in the treatment of GBM. RNA-pulsed dendritic cell vaccines have been shown to be safe in a small phase I clinical trial and RNA-loaded nanoparticle vaccines will soon be underway in GBM patients (NCT04573140).

Keywords: Dendritic cells; Glioblastoma; Immunotherapy; Nanoparticles; RNA; Vaccine.

Conflict of interest statement

This manuscript discusses patented technologies by EJS and DAM that are under option to license by iOncologi, Inc., and patents by DAM that have been licensed to Immunomic Therapeutics, Inc., Annias Immunotherapeutics, Inc., and Celldex, Inc.

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Figures

Fig. 1
Fig. 1
RNA-pulsed dendritic cell vaccines for GBM
Fig. 2
Fig. 2
Illustration of RNA nanoparticle immunotherapy

References

    1. Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. New England Journal of Medicine. 2020;383(25):2427–2438. doi: 10.1056/NEJMoa2028436.
    1. Bonehill A, Heirman C, Tuyaerts S, Michiels A, Breckpot K, Brasseur F, et al. Messenger RNA-electroporated dendritic cells presenting MAGE-A3 simultaneously in HLA class I and class II molecules. The Journal of Immunology. 2004;172(11):6649–6657. doi: 10.4049/jimmunol.172.11.6649.
    1. Chongsathidkiet P, Jackson C, Koyama S, Loebel F, Cui X, Farber SH, et al. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nature Medicine. 2018;24(9):1459–1468. doi: 10.1038/s41591-018-0135-2.
    1. Ding L, Li J, Wu C, Yan F, Li X, Zhang S. A self-assembled RNA-triple helix hydrogel drug delivery system targeting triple-negative breast cancer. Journal of Materials Chemistry B. 2020;8(16):3527–3533. doi: 10.1039/C9TB01610D.
    1. Dunn-Pirio, A., Peters, K., DesJardins, A., Randazzo, D., Friedman, H., Healy, P., et al. (2017). Tumor stem cell RNA-loaded dendritic cell vaccine for recurrent glioblastoma: A phase 1 trial (S41. 004). AAN Enterprises.
    1. Grippin AJ, Wummer B, Wildes T, Dyson K, Trivedi V, Yang C, et al. Dendritic cell-activating magnetic nanoparticles enable early prediction of antitumor response with magnetic resonance imaging. ACS Nano. 2019;13(12):13884–13898. doi: 10.1021/acsnano.9b05037.
    1. Insug O, Ku G, Ertl H, Blaszczyk-Thurin M. A dendritic cell vaccine induces protective immunity to intracranial growth of glioma. Anticancer Research. 2002;22(2A):613–621.
    1. Jin J, Bae KH, Yang H, Lee SJ, Kim H, Kim Y, et al. In vivo specific delivery of c-Met siRNA to glioblastoma using cationic solid lipid nanoparticles. Bioconjugate Chemistry. 2011;22(12):2568–2572. doi: 10.1021/bc200406n.
    1. Kobayashi T, Yamanaka R, Homma J, Tsuchiya N, Yajima N, Yoshida S, et al. Tumor mRNA-loaded dendritic cells elicit tumor-specific CD8+ cytotoxic T cells in patients with malignant glioma. Cancer Immunology Immunotherapy. 2003;52(10):632–637. doi: 10.1007/s00262-003-0408-5.
    1. Learn CA, Fecci PE, Schmittling RJ, Xie W, Karikari I, Mitchell DA, et al. Profiling of CD4+, CD8+, and CD4+CD25+CD45RO+FoxP3+ T cells in patients with malignant glioma reveals differential expression of the immunologic transcriptome compared with T cells from healthy volunteers. Clinical Cancer Research. 2006;12(24):7306–7315. doi: 10.1158/1078-0432.CCR-06-1727.
    1. Mitchell DA, Batich KA, Gunn MD, Huang M-N, Sanchez-Perez L, Nair SK, et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature. 2015;519(7543):366–369. doi: 10.1038/nature14320.
    1. Mitchell DA, Sayour EJ, Reap E, Schmittling R, DeLeon G, Norberg P, et al. Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide. Cancer Immunology Research. 2015;3(4):320–325. doi: 10.1158/2326-6066.CIR-14-0100.
    1. Mitchell DA, Xie W, Schmittling R, Learn C, Friedman A, McLendon RE, et al. Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro-Oncology. 2008;10(1):10–18. doi: 10.1215/15228517-2007-035.
    1. Rahman M, Ghiaseddin A, Yegorov O, Yang C, Dechkovskaia A, Tran D, et al. ATIM-15. Sustained complete radiographic response and prolonged systemic immune activation in a patient with MGMT unmethylated midline glioblastoma receiving CMV pp65-LAMP RNA-pulsed dendritic cell vaccines. Neuro-oncology. 2019;21:vi4. doi: 10.1093/neuonc/noz175.015.
    1. Sahin U, Muik A, Derhovanessian E, Vogler I, Kranz LM, Vormehr M, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature. 2020;586(7830):594–599. doi: 10.1038/s41586-020-2814-7.
    1. Sayour EJ, De Leon G, Pham C, Grippin A, Kemeny H, Chua J, et al. Systemic activation of antigen-presenting cells via RNA-loaded nanoparticles. Oncoimmunology. 2016 doi: 10.1080/2162402X.2016.1256527.
    1. Sayour EJ, Grippin A, De Leon G, Stover B, Rahman M, Karachi A, et al. Personalized tumor RNA loaded lipid-nanoparticles prime the systemic and intratumoral milieu for response to cancer immunotherapy. Nano Letters. 2018 doi: 10.1021/acs.nanolett.8b02179.
    1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine. 2005;352(10):987–996. doi: 10.1056/NEJMoa043330.
    1. Yaghi NK, Wei J, Hashimoto Y, Kong L-Y, Gabrusiewicz K, Nduom EK, et al. Immune modulatory nanoparticle therapeutics for intracerebral glioma. Neuro-Oncology. 2017;19(3):372–382.
    1. Zhang F, Parayath N, Ene C, Stephan S, Koehne A, Coon M, et al. Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers. Nature Communications. 2019;10(1):1–16. doi: 10.1038/s41467-018-07882-8.

Source: PubMed

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