The tumor-associated antigen RHAMM (HMMR/CD168) is expressed by monocyte-derived dendritic cells and presented to T cells
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Yannick Willemen1, Johan M.J. Van den Bergh1, Sarah M. Bonte2, Sébastien Anguille1, Carlo Heirman3, Barbara M.H. Stein1, Herman Goossens4, Tessa Kerre2, Kris Thielemans3, Marc Peeters5, Viggo F.I. Van Tendeloo1, Evelien L.J. Smits1,5,*, Zwi N. Berneman1,*
1Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
2Department of Hematology and Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium
3Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium
4Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
5Center for Oncological Research, University of Antwerp, Antwerp, Belgium
*Shared senior authors
Yannick Willemen, email: [email protected]
Keywords: electroporation, hyaluronan-mediated motility receptor, immunotherapy, messenger RNA, vaccination
Received: January 26, 2016 Accepted: September 12, 2016 Published: September 21, 2016
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.
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