In vivo potential of recombinant granulysin against human melanoma

Cancer Treat Res Commun. 2021:27:100355. doi: 10.1016/j.ctarc.2021.100355. Epub 2021 Mar 19.

Abstract

9-kDa granulysin is a protein expressed into the granules of human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. It has been shown to exert cytolysis on microbes and tumors. We showed previously that 9-kDa granulysin exerted cell death by apoptosis in vitro on hematological tumor cell lines and also on cells from B-cell chronic lymphocytic leukemia (B-CLL) patients. In addition, we have shown the anti-tumor efficiency of granulysin as a single agent in two in vivo models of human tumor development in athymic mice, the MDA-MB-231 mammary adenocarcinoma and the NCI-H929 multiple myeloma, without signs of overt secondary effects by itself. In this work, we have tested recombinant 9-kDa granulysin in an in vivo and especially aggressive model of melanoma development, xenografted UACC62 cells in athymic mice. Recombinant granulysin was administered once UACC62-derived tumors were detectable and it substantially retarded the in vivo development of this aggressive tumor. We could also detect apoptosis induction and increased NK cell infiltration inside granulysin-treated tumor tissues. These observations are especially interesting given the possibility of treating melanoma by intra-tumor injection.

Keywords: Apoptosis; Athymic mice; Granulysin; Intra-tumor; Melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / pharmacology
  • Antigens, Differentiation, T-Lymphocyte / therapeutic use*
  • Apoptosis / drug effects
  • Calreticulin / metabolism
  • Cell Line, Tumor
  • Humans
  • Killer Cells, Natural
  • Lymphocytes, Tumor-Infiltrating
  • Male
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / pathology
  • Mice
  • Neoplasm Transplantation
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Calreticulin
  • GNLY protein, human
  • Recombinant Proteins