Induction of cellular immunity by anti-idiotypic antibodies mimicking GD2 ganglioside.
Gangliosides are potentially useful targets for tumor destruction by antibodies. However, the role of gangliosides in T cell-mediated immunity to tumors is unclear. We produced three murine monoclonal anti-idiotypic antibodies (Ab2) against a monoclonal antibody (Ab1) that binds strongly to melanoma-associated GD2 ganglioside and weakly to GD3 ganglioside. All three Ab2 induced anti-anti-idiotypic antibodies (Ab3) with Ab1-like binding specificity to tumor cells and antigen in rabbits. The Ab3 specifically bound to GD2(+) tumor cells and isolated GD2, and shared idiotopes with the Ab1. Two of the three Ab2 induced GD2-specific delayed-type hypersensitivity responses in BALB/c and C57BL/6 mice, but not in C57BL/6/CD4(-/-) mice. Peripheral blood mononuclear cells (PBMC) from a melanoma patient proliferated specifically in response to in vitro stimulation with Ab2. Proliferation was accompanied by Th1-type cytokine production. Our studies demonstrate the induction of ganglioside-specific T cell-dependent immunity by Ab2 in mice. These T cells showed specific reactivity to ganglioside expressed by tumor cells.
Basak
Saroj
S
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, USA.
Birebent
Brigitte
B
Purev
Enkhtsetseg
E
Somasundaram
Rajasekharan
R
Maruyama
Haruhiko
H
Zaloudik
Jan
J
Swoboda
Rolf
R
Strittmatter
Wolfgang
W
Li
Weiping
W
Luckenbach
Albrecht
A
Song
Hong
H
Li
Jian
J
Sproesser
Katrin
K
Guerry
Dupont
D
Nair
Sridar
S
Furukawa
Koichi
K
Herlyn
Dorothee
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D005732:Gangliosides / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D007130:Immunoglobulin Idiotypes / Q000737:chemistry; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008545:Melanoma / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D011817:Rabbits; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D001616:beta-Galactosidase / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D007130:Immunoglobulin Idiotypes; C019403:ganglioside, GD2; D001616:beta-Galactosidase