Murine dendritic cells pulsed with an anti-idiotype antibody induce antigen-specific protective antitumor immunity.
In this study, using the carcinoembryonic antigen (CEA)-expressing C15 murine colon carcinoma system in syngeneic C57BL/6 mice, we have evaluated the efficacy of bone marrow-derived dendritic cells (DCs) pulsed with the murine anti-idiotype antibody 3H1 as a tumor vaccine. Anti-idiotype 3H1 mimics a distinct and specific epitope of CEA and can generate anti-CEA immunity in mice, rabbits, monkeys, and humans when used with a conventional immune adjuvant. Our goal was to determine whether the use of DC as direct antigen-presenting cells would improve the potency of 3H1 as vaccine. Bone marrow-DC pulsed with 3H1 and injected into naïve mice induced both humoral and cellular anti-3H1, as well as anti-CEA immunity. Specific killing of C15 cells in in vitro antibody-dependent cellular cytotoxicity has been observed by immune sera. Immune-splenic lymphocytes when stimulated in vitro with 3H1 or CEA, showed increased proliferative CD4(+) Th1 type T-cell response and secreted significantly high levels of Th1 cytokines [IFN-gamma, interleukin (IL)-2] and low levels of Th2 cytokines (IL-4, IL-10). This vaccine also induced MHC class I antigen-restricted CD8(+) T-cell responses. The up-regulation of activation markers CD69 and CD25 on CD8(+) CTLs correlated with antigen-specific strong CTL responses in vitro. The immunity induced in mice resulted in a complete rejection of CEA-expressing C15 tumor cells in 100% of experimental mice, whereas no protection was observed when 3H1-pulsed DC-vaccinated mice were challenged with CEA-negative MC-38 cells. The tumor rejection in 3H1-pulsed DC-treated mice was associated with the induction of a memory response that helped those mice to survive a second challenge with a lethal dose of C15 cells.
Saha
Asim
A
Department of Internal Medicine and the Barrett Cancer Center, University of Cincinnati, Cincinnati, Ohio 45267, USA.
Chatterjee
Sunil K
SK
Foon
Kenneth A
KA
Primus
F James
FJ
Bhattacharya-Chatterjee
Malaya
M
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D018664:Interleukin-12