Brief Communication: Combination of an MIP3α-Antigen Fusion Therapeutic DNA Vaccine With Treatments of IFNα and 5-Aza-2'Deoxycytidine Enhances Activated Effector CD8+ T Cells Expressing CD11c in the B16F10 Melanoma Model

J Immunother. 2025 Jan 1;48(1):1-5. doi: 10.1097/CJI.0000000000000542. Epub 2024 Oct 14.

Abstract

Previous studies in the B16F10 mouse melanoma model have demonstrated that combining a DNA vaccine comprised of regions of gp100 and tyrosinase-related protein 2 fused to macrophage-inflammatory protein 3-alpha (MIP3α) with recombinant interferon alpha (IFN) and 5-Aza-2'-deoxycytidine (5Aza) treatments resulted in significantly greater antitumor activity and immunogenicity in the tumor microenvironment (TME). This brief report details that the combination of vaccine with treatments IFN and 5Aza results in an increase in the TME of a distinct CD11c+ CD8+ T-cell population. This cell population correlates with tumor size, is primarily comprised of effector or effector memory T cells, and has a more robust response to ex vivo stimulation as compared with CD11c- CD8+ T cells. In conclusion, this combination therapy results in a greater presence of highly active effector CD8+ T cells expressing CD11c in the TME, which are likely primary contributors to treatment efficacy.

MeSH terms

  • Animals
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • CD11c Antigen* / metabolism
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / metabolism
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Decitabine* / pharmacology
  • Decitabine* / therapeutic use
  • Disease Models, Animal
  • Humans
  • Interferon-alpha*
  • Intramolecular Oxidoreductases
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Melanoma, Experimental* / immunology
  • Melanoma, Experimental* / therapy
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Fusion Proteins / pharmacology
  • Tumor Microenvironment* / drug effects
  • Tumor Microenvironment* / immunology
  • Vaccines, DNA*
  • gp100 Melanoma Antigen

Substances

  • Decitabine
  • Vaccines, DNA
  • CD11c Antigen
  • Interferon-alpha
  • Cancer Vaccines
  • Recombinant Fusion Proteins
  • dopachrome isomerase
  • gp100 Melanoma Antigen
  • Azacitidine
  • Intramolecular Oxidoreductases