TLR Agonist rHP-NAP as an Adjuvant of Dendritic Cell-Based Vaccine to Enhance Anti-Melanoma Response

Iran J Immunol. 2020 Mar;17(1):14-25. doi: 10.22034/iji.2020.80291.

Abstract

Background: Melanoma is a common and malignant cutaneous tumor, which is responsible for a large proportion of skin cancer deaths. Dendritic cell (DC)-based vaccines have achieved positive results in the treatment of melanoma because of their ability to induce cytotoxic response to facilitate tumor elimination.

Objective: To improve the efficacy of dendritic cell-based vaccines by the adjuvant activity of Helicobacter pylori neutrophil activating protein (HP-NAP).

Methods: The recombinant HP-NAP (rHP-NAP) was expressed by using prokaryotic expression system. DCs were cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. After treating with rHP-NAP, the maturation of DCs and dendritic cell-based vaccine were assayed by using flow cytometry and qRT-PCR. The activation and proliferation of T cells were measured by FCM, ELISA and MTT methods. The tumor specific cytotoxic response to resistant B16F10 was detected by using lactate dehydrogenase-release assay and qRT-PCR.

Results: The rHP-NAP, prepared from E. coli prokaryotic expression system, was able to significantly promote the maturation of dendritic cell-based vaccine loaded with tumor cell lysate (TCL) of B16F10 (DC-B16F10-TCL). Furthermore, it effectively induced the activation and proliferation of T cells and tumor specific cytotoxic response to resistant B16F10 melanoma tumor cells.

Conclusion: These results suggested that rHP-NAP possesses the potential for use as an adjuvant of dendritic cell-based vaccine in anti-melanoma treatment.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Bacterial Proteins / immunology
  • Bacterial Proteins / pharmacology*
  • Cancer Vaccines / immunology
  • Cancer Vaccines / pharmacology*
  • Dendritic Cells / transplantation*
  • Humans
  • Melanoma, Experimental*
  • Mice, Inbred C57BL
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Toll-Like Receptors / agonists

Substances

  • Adjuvants, Immunologic
  • Bacterial Proteins
  • Cancer Vaccines
  • Recombinant Proteins
  • Toll-Like Receptors
  • neutrophil-activating protein A, Helicobacter pylori