Synergistic cancer immunotherapy combines MVA-CD40L induced innate and adaptive immunity with tumor targeting antibodies

Nat Commun. 2019 Nov 6;10(1):5041. doi: 10.1038/s41467-019-12998-6.


Virus-based vaccines and appropriate costimulation potently enhance antigen-specific T cell immunity against cancer. Here we report the use of recombinant modified vaccinia virus Ankara (rMVA) encoding costimulatory CD40L against solid tumors. Therapeutic treatment with rMVA-CD40L-expressing tumor-associated antigens results in the control of established tumors. The expansion of tumor-specific cytotoxic CD8+ T cells is essential for the therapeutic antitumor effects. Strikingly, rMVA-CD40L also induces strong natural killer (NK) cell activation and expansion. Moreover, the combination of rMVA-CD40L and tumor-targeting antibodies results in increased therapeutic antitumor efficacy relying on the presence of Fc receptor and NK cells. We describe a translationally relevant therapeutic synergy between systemic viral vaccination and CD40L costimulation. We show strengthened antitumor immune responses when both rMVA-CD40L-induced innate and adaptive immune mechanisms are exploited by combination with tumor-targeting antibodies. This immunotherapeutic approach could translate into clinical cancer therapies where tumor-targeting antibodies are employed.

MeSH terms

  • Adaptive Immunity*
  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Antibodies, Neoplasm / immunology*
  • Antineoplastic Agents / therapeutic use
  • CD40 Ligand / pharmacology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Drug Synergism
  • Female
  • Humans
  • Immunity, Innate*
  • Immunization
  • Immunotherapy / methods*
  • Killer Cells, Natural / immunology
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Vaccination
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / therapeutic use
  • Viral Vaccines / therapeutic use*


  • Adjuvants, Immunologic
  • Antibodies, Neoplasm
  • Antineoplastic Agents
  • Cancer Vaccines
  • Vaccines, Synthetic
  • Viral Vaccines
  • CD40 Ligand