Transforming the prostatic tumor microenvironment with oncolytic virotherapy Academic Article uri icon

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abstract

  • Prostate cancer (PCa) was estimated to have the second highest global incidence rate for male non-skin tumors and is the fifth most deadly in men thus mandating the need for novel treatment options. MG1-Maraba is a potent and versatile oncolytic virus capable of lethally infecting a variety of prostatic tumor cell lines alongside primary PCa biopsies and exerts direct oncolytic effects against large TRAMP-C2 tumors in vivo. An oncolytic immunotherapeutic strategy utilizing a priming vaccine and intravenously administered MG1-Maraba both expressing the human six-transmembrane antigen of the prostate (STEAP) protein generated specific CD8+ T-cell responses against multiple STEAP epitopes and resulted in functional breach of tolerance. Treatment of mice with bulky TRAMP-C2 tumors using oncolytic STEAP immunotherapy induced an overt delay in tumor progression, marked intratumoral lymphocytic infiltration with an active transcriptional profile and up-regulation of MHC class I. The preclinical data generated here offers clear rationale for clinically evaluating this approach for men with advanced PCa.

authors

  • Atherton, Matthew J
  • Stephenson, Kyle B
  • Tzelepis, Fanny
  • Bakhshinyan, David
  • Nikota, Jake K
  • Son, Hwan Hee
  • Jirovec, Anna
  • Lefebvre, Charles
  • Dvorkin-Gheva, Anna
  • Ashkar, Ali A
  • Wan, Yonghong
  • Stojdl, David F
  • Belanger, Eric C
  • Breau, Rodney H
  • Bell, John C
  • Saad, Fred
  • Singh, Sheila K
  • Diallo, Jean-Simone
  • Lichty, Brian

publication date

  • July 3, 2018