Anti-tumor efficacy of plasmid encoding emm55 in a murine melanoma model

Cancer Immunol Immunother. 2020 Dec;69(12):2465-2476. doi: 10.1007/s00262-020-02634-4. Epub 2020 Jun 18.

Abstract

Emm55 is a bacterial gene derived from Streptococcus pyogenes (S. pyogenes) that was cloned into a plasmid DNA vaccine (pAc/emm55). In this study, we investigated the anti-tumor efficacy of pAc/emm55 in a B16 murine melanoma model. Intralesional (IL) injections of pAc/emm55 significantly delayed tumor growth compared to the pAc/Empty group. There was a significant increase in the CD8+ T cells infiltrating into the tumors after pAc/emm55 treatment compared to the control group. In addition, we observed that IL injection of pAc/emm55 increased antigen-specific T cell infiltration into tumors. Depletion of CD4+ or CD8+ T cells abrogated the anti-tumor effect of pAc/emm55. Combination treatment of IL injection of pAc/emm55 with anti-PD-1 antibody significantly delayed tumor growth compared to either monotherapy. pAc/emm55 treatment combined with PD-1 blockade enhanced anti-tumor immune response and improved systemic anti-tumor immunity. Together, these strategies may lead to improvements in the treatment of patients with melanoma.

Keywords: Bacterial protein; Intralesional injection; Melanoma; Streptococcus pyogenes; emm55.

MeSH terms

  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor / transplantation
  • Combined Modality Therapy / methods
  • Female
  • Humans
  • Immunotherapy / methods*
  • Injections, Intralesional
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Plasmids / administration & dosage
  • Plasmids / genetics
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology

Substances

  • Antigens, Bacterial
  • Antineoplastic Agents, Immunological
  • Bacterial Outer Membrane Proteins
  • Emm55 protein, Streptococcus pyogenes
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor