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Clinical trials of self-replicating RNA-based cancer vaccines.

Publication ,  Journal Article
Morse, MA; Crosby, EJ; Force, J; Osada, T; Hobeika, AC; Hartman, ZC; Berglund, P; Smith, J; Lyerly, HK
Published in: Cancer Gene Ther
June 2023

Therapeutic cancer vaccines, designed to activate immune effectors against tumor antigens, utilize a number of different platforms for antigen delivery. Among these are messenger RNAs (mRNA), successfully deployed in some prophylactic SARS-CoV2 vaccines. To enhance the immunogenicity of mRNA-delivered epitopes, self-replicating RNAs (srRNA) that markedly increase epitope expression have been developed. These vectors are derived from positive-strand RNA viruses in which the structural protein genes have been replaced with heterologous genes of interest, and the structural proteins are provided in trans to create single cycle viral replicon particles (VRPs). Clinical stage srRNA vectors have been derived from alphaviruses, including Venezuelan Equine Encephalitis (VEE), Sindbis, and Semliki Forest virus (SFV) and have encoded the tumor antigens carcinoembryonic antigen (CEA), human epidermal growth factor receptor 2 (HER2), prostate specific membrane antigen (PSMA), and human papilloma virus (HPV) antigens E6 and E7. Adverse events have mainly been grade 1 toxicities and minimal injection site reactions. We review here the clinical experience with these vaccines and our recent safety data from a study combining a VRP encoding HER2 plus an anti-PD1 monoclonal antibody (pembrolizumab). This experience with VRP-based srRNA supports recent development of fully synthetic srRNA technologies, where the viral structural proteins are replaced with protective lipid nanoparticles (LNP), cationic nanoemulsions or polymers.

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Published In

Cancer Gene Ther

DOI

EISSN

1476-5500

Publication Date

June 2023

Volume

30

Issue

6

Start / End Page

803 / 811

Location

England

Related Subject Headings

  • SARS-CoV-2
  • Replicon
  • RNA, Viral
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Neoplasms
  • Humans
  • Genetic Vectors
  • Encephalitis Virus, Venezuelan Equine
  • Cancer Vaccines
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Morse, M. A., Crosby, E. J., Force, J., Osada, T., Hobeika, A. C., Hartman, Z. C., … Lyerly, H. K. (2023). Clinical trials of self-replicating RNA-based cancer vaccines. Cancer Gene Ther, 30(6), 803–811. https://doi.org/10.1038/s41417-023-00587-1
Morse, Michael A., Erika J. Crosby, Jeremy Force, Takuya Osada, Amy C. Hobeika, Zachary C. Hartman, Peter Berglund, Jonathan Smith, and H Kim Lyerly. “Clinical trials of self-replicating RNA-based cancer vaccines.Cancer Gene Ther 30, no. 6 (June 2023): 803–11. https://doi.org/10.1038/s41417-023-00587-1.
Morse MA, Crosby EJ, Force J, Osada T, Hobeika AC, Hartman ZC, et al. Clinical trials of self-replicating RNA-based cancer vaccines. Cancer Gene Ther. 2023 Jun;30(6):803–11.
Morse, Michael A., et al. “Clinical trials of self-replicating RNA-based cancer vaccines.Cancer Gene Ther, vol. 30, no. 6, June 2023, pp. 803–11. Pubmed, doi:10.1038/s41417-023-00587-1.
Morse MA, Crosby EJ, Force J, Osada T, Hobeika AC, Hartman ZC, Berglund P, Smith J, Lyerly HK. Clinical trials of self-replicating RNA-based cancer vaccines. Cancer Gene Ther. 2023 Jun;30(6):803–811.

Published In

Cancer Gene Ther

DOI

EISSN

1476-5500

Publication Date

June 2023

Volume

30

Issue

6

Start / End Page

803 / 811

Location

England

Related Subject Headings

  • SARS-CoV-2
  • Replicon
  • RNA, Viral
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Neoplasms
  • Humans
  • Genetic Vectors
  • Encephalitis Virus, Venezuelan Equine
  • Cancer Vaccines