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- Title
Linkage of CD40L to a self-tumor antigen enhances the antitumor immune responses of dendritic cell-based treatment.
- Authors
Chen, Hsin-Wei; Huang, Hsing-I; Lee, Yi-Ping; Chen, Li-Li; Liu, Hsiung-Kun; Cheng, Mei-Lien; Tsai, Jy-Ping; Tao, Mi-Hua; Ting, Chou-Chik
- Abstract
CD40–CD40 ligand (CD40L) interaction is an important costimulatory signal in the interaction between T cells and antigen-presenting cells (APC). In the present study, we determined whether the linkage of CD40L to the tumor-specific idiotype (Id) derived from a murine B-cell lymphoma, 38C13, could enhance its immunogenicity when presented by dendritic cells (DC). We showed that bone marrow-derived DC pulsed with Id-CD40L upregulated the expression of CD40, CD80, CD86, and major histocompatibility complex (MHC) class II molecules with the increased production of interleukin-12 (IL-12). Mice immunized with DC loaded with Id-CD40L showed high levels of anti-Id antibody response of both IgG2a and IgG1 isotypes. In addition, nylon wool-enriched T cells from these immunized mice showed a tumor-specific T-cell proliferative response upon stimulation with Id protein. Mice immunized with DC pulsed with Id alone failed to show any of these immune responses. Immunization with DC pulsed with Id-CD40L showed increased resistance to the challenge by 38C13 tumor, and tumor growth was significantly retarded. Together, these results show that linkage of CD40L to a self-tumor antigen enhances the anti-tumor immune response in DC-based treatment.
- Subjects
LIGANDS (Biochemistry); TUMOR antigens; IMMUNE response; DENDRITIC cells; ANTIGEN presenting cells; IMMUNOTHERAPY; CANCER vaccines; VACCINES
- Publication
Cancer Immunology, Immunotherapy, 2002, Vol 51, Issue 6, p341
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-002-0283-5