The tumor-associated antigen RHAMM (HMMR/CD168) is expressed by monocyte-derived dendritic cells and presented to T cells

Oncotarget. 2016 Nov 8;7(45):73960-73970. doi: 10.18632/oncotarget.12170.

Abstract

We formerly demonstrated that vaccination with Wilms' tumor 1 (WT1)-loaded autologous monocyte-derived dendritic cells (mo-DCs) can be a well-tolerated effective treatment in acute myeloid leukemia (AML) patients. Here, we investigated whether we could introduce the receptor for hyaluronic acid-mediated motility (RHAMM/HMMR/CD168), another clinically relevant tumor-associated antigen, into these mo-DCs through mRNA electroporation and elicit RHAMM-specific immune responses. While RHAMM mRNA electroporation significantly increased RHAMM protein expression by mo-DCs, our data indicate that classical mo-DCs already express and present RHAMM at sufficient levels to activate RHAMM-specific T cells, regardless of electroporation. Moreover, we found that RHAMM-specific T cells are present at vaccination sites in AML patients. Our findings implicate that we and others who are using classical mo-DCs for cancer immunotherapy are already vaccinating against RHAMM.

Keywords: electroporation; hyaluronan-mediated motility receptor; immunotherapy; messenger RNA; vaccination.

MeSH terms

  • Antigen Presentation / immunology*
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Electroporation
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / immunology*
  • Gene Expression
  • HLA-A Antigens / immunology
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / immunology*
  • Immunotherapy
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / therapy
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Extracellular Matrix Proteins
  • HLA-A Antigens
  • Hyaluronan Receptors
  • RNA, Messenger
  • hyaluronan-mediated motility receptor