Immunoselection of functional CMRF-56+ blood dendritic cells from multiple myeloma patients for immunotherapy.
Dendritic cells (DCs) loaded with tumor-associated antigens are a promising treatment to prevent disease relapse in patients with multiple myeloma (MM). Early-phase clinical trials have shown safety, efficacy, and immunologic responses in MM, but a key issue now is the isolation of a functional, clinically relevant DC preparation. The authors have described a unique blood DC (BDC) isolation platform based on positive immunoselection with the CMRF-56 antibody. To validate this as a feasible source of BDCs for immunotherapy, the authors undertook a quantitative and functional analysis of BDCs in MM patients and healthy donors. These data show that MM patients have similar numbers of CD11c+CD16+ and CD11c+CD16- BDCs but about half the number of CD11c-CD123+ BDCs in whole blood compared with healthy donors. BDCs could be isolated by CMRF-56+ immunoselection from all MM patients tested, with similar yields and purity to healthy donors. These BDCs could be activated ex vivo with poly I:C or LPS. Furthermore, CMRF-56+ preparations could induce potent CD4+ and CD8+ T-lymphocyte responses in both MM patients and healthy donors. These data suggest that BDCs with in vitro functional integrity can be isolated from MM patients in sufficient numbers to justify a clinical trial.
Radford
Kristen J
KJ
Mater Medical Research Institute, South Brisbane 4101, Australia.
Turtle
Cameron J
CJ
Kassianos
Andrew J
AJ
Vuckovic
Slavica
S
Gardiner
Damien
D
Khalil
Dahlia
D
Taylor
Kerry
K
Wright
Sue
S
Gill
Devinder
D
Hart
Derek N J
DN
D000368:Aged; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000276:immunology*; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D039521:CD11c Antigen / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D053650:Interleukin-3 Receptor alpha Subunit; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy; D011070:Poly I-C / Q000494:pharmacology; D016185:Receptors, Interleukin-3 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D039521:CD11c Antigen; C119956:CMRF-56 antigen; D016207:Cytokines; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D008070:Lipopolysaccharides; D016185:Receptors, Interleukin-3; D007371:Interferon-gamma; D011070:Poly I-C