Linkage of CD40L to a self-tumor antigen enhances the antitumor immune responses of dendritic cell-based treatment.
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.
Chen
Hsin-Wei
HW
Immunology Group, National Health Research Institutes, Taipei, Taiwan.
Huang
Hsing-I
HI
Lee
Yi-Ping
YP
Chen
Li-Li
LL
Liu
Hsiung-Kun
HK
Cheng
Mei-Lien
ML
Tsai
Jy-Ping
JP
Tao
Mi-Hua
MH
Ting
Chou-Chik
CC
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D005260:Female; D007114:Immunization; D007117:Immunization, Secondary; D018796:Immunoconjugates / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D011993:Recombinant Fusion Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C464525:Id tumor-specific protein, mouse; D018796:Immunoconjugates; D011993:Recombinant Fusion Proteins; D023201:CD40 Ligand; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma