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- Title
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.
- Authors
Fujisawa, Yasuhiro; Nabekura, Tsukasa; Nakao, Tomohei; Nakamura, Yasuhiro; Takahashi, Takenori; Kawachi, Yasuhiro; Otsuka, Fujio; Onodera, Masafumi
- Abstract
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.
- Subjects
T cells; CELL lines; IMMUNOTHERAPY; DENDRITIC cells; ANTIGENS
- Publication
Experimental Dermatology, 2009, Vol 18, Issue 4, p396
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/j.1600-0625.2008.00802.x