N-dihydrogalactochitosan as immune and direct antitumor agent amplifying the effects of photodynamic therapy and photodynamic therapy-generated vaccines

Int Immunopharmacol. 2019 Oct:75:105764. doi: 10.1016/j.intimp.2019.105764. Epub 2019 Jul 25.

Abstract

It is becoming apparent that to obtain robust and prolonged antitumor responses in cancer immunotherapy, appropriate adjunct agents promoting both tumor antigen delivery and immune rejection enhancement are critically required. The semisynthetic biopolymer N-dihydrogalactochitosan (GC) is emerging as a promising such candidate. In the present study, the effects of GC were investigated when combined with cancer vaccines generated by photodynamic therapy (PDT) using mouse tumor model SCCVII (squamous cell carcinoma). The adjunct GC treatment was found to enhance therapeutic benefit obtained with PDT vaccine, while reducing the numbers of myeloid-derived suppressor cells. Another important property of GC is promoting directly the death of SCCVII cells sustaining injury from PDT mediated by various photosensitizers. This effect is extended to cells treated by cryoablation therapy (CAT) performed by exposure to -80 °C. A capacity of GC for preferential binding to PDT treated cells was demonstrated using fluorescence microscopy. In vitro testing with specific caspase-1 inhibitor revealed a pro-survival role of this enzyme in membrane lipid repair mechanisms following combined PDT plus GC treatment. In conclusion, GC represents a uniquely promising adjunct for various PDT protocols, photothermal and similar rapid tumor-ablating therapies.

Keywords: Cryoablation therapy; Glycated chitosan; Immunoadjuvant; Immunoregulatory cells; Photodynamic therapy; SCCVII tumor cells.

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cancer Vaccines / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Chitosan / analogs & derivatives*
  • Chitosan / therapeutic use*
  • Cryosurgery
  • Head and Neck Neoplasms / drug therapy*
  • Immunotherapy
  • Mice, Inbred C3H
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use
  • Tumor Cells, Cultured

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Cancer Vaccines
  • Photosensitizing Agents
  • Chitosan