CMRF-56 Immunoselected Blood Dendritic Cell Preparations... : Journal of Immunotherapy (original) (raw)

Basic Studies

CMRF-56 Immunoselected Blood Dendritic Cell Preparations Activated With GM-CSF Induce Potent Antimyeloma Cytotoxic T-cell Responses

*Mater Medical Research Institute, South Brisbane

†University of Queensland, St Lucia, Queensland, Australia

Sources of Support: Multiple Myeloma Research Foundation, Leukaemia Foundation of Australia, Mater Medical Research Institute.

Financial Disclosure: The authors have declared there are no financial conflicts of interest with regard to this work.

Reprints: Derek N. J. Hart, Mater Medical Research Institute, Level 3 Aubigny Place, Raymond Tce, South Brisbane, 4101, Queensland, Australia (e-mail: [email protected]).

Received for publication December 22, 2006; accepted June 15, 2007

Abstract

The efficient antigen-presenting function of dendritic cells (DC) makes them an attractive cellular adjuvant for clinical immunotherapeutic protocols aimed at eradicating minimal residual disease after conventional treatment of multiple myeloma (MM) and other malignancies. We used single-step positive immunoselection with biotinylated CMRF-56 monoclonal antibody to generate a CD11c+ blood DC (BDC) enriched antigen-presenting cell population, which, after exposure to activation stimuli for as little as 2 hours, displayed a mature costimulatory BDC phenotype and secreted inflammatory cytokines. Of the activation stimuli tested, granulocyte macrophage colony-stimulating factor (GM-CSF) provided optimal activation of the CMRF-56 immunoselected preparations and primed efficient cytotoxic T cell (CTL) responses using MART-1 peptide as a model tumor-associated antigen. In addition, GM-CSF activated CMRF-56 immunoselected cells cross-presented MM cell lysate and improved the MM-specific polyclonal CTL response (no activation 18.8%±4.3% vs. GM-CSF activation 40.9%±7.3%, _P_=0.051). CMRF-56 immunoselected BDC migrated in vitro both spontaneously and specifically toward the secondary lymphoid chemokine CCL21. Their migration was also significantly improved by GM-CSF and prostaglandin E2 activation and a greater percentage of activated BDC migrated specifically compared with monocyte-derived DC. These results indicate that the CMRF-56 immunoselected BDC preparations can cross-present antigen for effective anti-MM CTL responses and that limited exposure to maturation stimuli can produce phenotypically and functionally mature migrating DC. CMRF-56 immunoselected cells are suitable for use as part of an immunotherapeutic anti-MM vaccine.