Combination of rAd-p53 in situ gene therapy and anti-PD-1 antibody immunotherapy induced anti-tumor activity in mouse syngeneic urogenital cancer models

• Kunimura, Naoto

• Kitagawa, Koichi

• Sako, Ryota

• Narikiyo, Keita

• Tominaga, Shoko

• Bautista, Diosdado S.

• Xu, Wei

• Fujisawa, Masato

• Shirakawa, Toshiro

Abstract

In this study we undertook a novel combination therapy using rAd-p53 in situ gene therapy and immunotherapy with immune checkpoint inhibitor (ICI) anti-PD-1 antibody for urogenital cancers. Three mouse syngeneic tumor cell lines, TRAMP-C2 (prostate cancer derived from C57BL/6 mice), MBT-2 (bladder cancer derived from C3H mice) and Renca (kidney cancer derived from BALB/c mice) were used in this study. The highest coxsackie and adenovirus receptor (CAR) mRNA expression was observed in TRAMP-C2 cells, followed by Renca and then MBT-2 cells. Consistent with the CAR expressions, rAd-p53 at 160 multiplicity of infection (MOI) significantly inhibited the cell proliferation of TRAMP-C2 and Renca cells, but not MBT-2 cells. In in vivo experiments, the combination of intratumoral injections of rAd-p53 (1x10(9) plaque-forming units) every other day and intraperitoneal injections of anti-mouse PD-1 antibody (200 μg) twice a week suppressed tumor growth and prolonged survival compared to rAd-p53 or anti-PD-1 antibody monotherapy in both the TRAMP-C2 and Renca models. Our results encourage the clinical development of combination therapy comprised of in situ gene therapy with rAd-p53 and immunotherapy with an ICI anti-PD-1 antibody for urogenital cancers.

Journal

• Scientific Reports

  Scientific Reports 10 (1), 17464-17464, 2020-10-15

  Nature Research

Details

• CRID: 1050294045368602240
• NII Article ID: 120006897865
• ISSN: 20452322
• HANDLE: 20.500.14094/90007618
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles