The induction of tumor-specific CD4+ T cells via major histocompatibility complex class II is required to gain optimal anti-tumor immunity against B16 melanoma cell line in tumor immunotherapy using dendritic cells.
We have demonstrated that dendritic cells (DCs) genetically modified to express tumor-associated antigens (TAAs) with retroviral vectors elicit more potential anti-tumor effect than those loaded with peptides because they can prime antigen-specific CD4+ T cells resulting in production of tumor-specific antibody. In this study, we showed the importance of antigen presentation via a major histocompatibility complex (MHC) class II molecule in cancer immunity against non-membrane bound TAAs such as the melanoma antigen gp100 by using DCs derived from MHC class II-deficient mice (C2KO). DCs were prepared by transduction of gp100 cDNA into haematopoietic progenitor cells obtained from C2KO followed by differentiation with cytokines (C2KO-gp/DCs). When C2KO-gp/DCs were inoculated into immunocompetent mice, the mice scarcely primed the antigen-specific Th1 cells and developed fewer CD8 T cells than did those inoculated with transduced DCs prepared from normal mice. The attenuated anti-tumor effect was also confirmed in a postimmunization setting where, while two of eight control mice eradicated the pre-existing melanoma cell line B16 (25%), no mice inoculated with C2KO-gp/DCs did. These results suggested not only the limitation of current protocols using MHC class I-restricted tumor peptides but also the usefulness of DCs expressing gp100 in vaccine therapy against melanoma.
Fujisawa
Yasuhiro
Y
Division of Clinical and Experimental Hematology, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Nabekura
Tsukasa
T
Nakao
Tomohei
T
Nakamura
Yasuhiro
Y
Takahashi
Takenori
T
Kawachi
Yasuhiro
Y
Otsuka
Fujio
F
Onodera
Masafumi
M
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology*; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D058951:gp100 Melanoma Antigen
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D006681:HLA-D Antigens; D008562:Membrane Glycoproteins; C548642:Pmel protein, mouse; D058951:gp100 Melanoma Antigen