Alpha-type 1-polarized dendritic cells loaded with apoptotic allogeneic myeloma cell line induce strong CTL responses against autologous myeloma cells.
To induce a potent cytotoxic T lymphocyte (CTL) response, various tumor antigens should be loaded onto dendritic cells (DCs). In multiple myeloma (MM), it is difficult to obtain a sufficient number of autologous tumor cells as a source of tumor antigens in the clinical setting. We investigated the feasibility of immunotherapy in patients with MM, using myeloma-specific CTLs generated in vitro by alpha-type 1-polarized DCs (alphaDC1s) loaded with the ultraviolet B-irradiated allogeneic myeloma cell line, ARH77. alphaDC1s significantly increased the expression of several costimulatory molecules without differences in loading with tumor antigens. alphaDC1s showed a high production of interleukin-12 during maturation and after subsequent stimulation with CD40L but were not significantly affected by loading tumor antigens. Myeloma-specific CTLs against autologous myeloma cells from MM patients were induced by alphaDC1s pulsed with apoptotic ARH77 cells. Our data indicate that autologous DCs loaded with an allogeneic myeloma cell line can generate potent myeloma-specific CTL responses against autologous myeloma cells and might provide a practical method for cellular immunotherapy in patients with MM.
Yang
Deok-Hwan
DH
Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeollanamdo, South Korea.
Kim
Mi-Hyun
MH
Hong
Cheol Yi
CY
Lee
Youn-Kyung
YK
Jin
Chun-Ji
CJ
Pham
Thanh-Nhan Nguyen
TN
Ahn
Jae-Sook
JS
Bae
Woo-Kyun
WK
Kim
Yeo-Kyeoung
YK
Chung
Ik-Joo
IJ
Kim
Hyeoung-Joon
HJ
Kalinski
Pawel
P
Lee
Je-Jung
JJ
D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D045744:Cell Line, Tumor / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous
D000951:Antigens, Neoplasm