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.
Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeollanamdo, South Korea.
Deok-Hwan
DH
Yang
Mi-Hyun
MH
Kim
Cheol Yi
CY
Hong
Youn-Kyung
YK
Lee
Chun-Ji
CJ
Jin
Thanh-Nhan Nguyen
TN
Pham
Jae-Sook
JS
Ahn
Woo-Kyun
WK
Bae
Yeo-Kyeoung
YK
Kim
Ik-Joo
IJ
Chung
Hyeoung-Joon
HJ
Kim
Pawel
P
Kalinski
Je-Jung
JJ
Lee
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