Genetic modification of oncolytic viruses to enhance antitumor immunity

Methods Enzymol. 2020;635:231-250. doi: 10.1016/bs.mie.2019.05.017. Epub 2019 Jun 11.


Among the many immunotherapies being developed and tested both preclinically and clinically, oncolytic viruses (OVs) are gaining traction as a forerunner in the search for potent new therapeutic agents, with a genetically engineered herpes simplex virus type 1 (HSV-1) recently approved by the FDA for the treatment of melanoma. The great potential of OVs to fight cancer is driving different approaches to improve OV-based therapy, with genetic modification of OVs to enhance host antitumor immunity being one of the most promising approaches. In this chapter we describe possible modifications in the OV genome that could increase its antitumor activity and immunostimulatory capacity, together with different methods to achieve these goals. Finally, we present different analyses to verify the desired genetic modification and evaluate its impact on host antitumor immunity in preliminary stages.

Keywords: Antitumor immune stimulation; Genetic modification; HSV-1; Homologous recombination; Immunotherapy; Oncolytic virus.

MeSH terms

  • Genetic Engineering
  • Humans
  • Immunotherapy
  • Neoplasms* / genetics
  • Neoplasms* / therapy
  • Oncolytic Virotherapy*
  • Oncolytic Viruses* / genetics