Induction of cellular immunity by anti-idiotypic antibodies mimicking GD2 ganglioside

被引:24
作者
Basak, S
Birebent, B
Purev, E
Somasundaram, R
Maruyama, H
Zaloudik, J
Swoboda, R
Strittmatter, W
Li, WP
Luckenbach, A
Song, H
Li, J
Sproesser, K
Guerry, D
Nair, S
Furukawa, K
Herlyn, D
机构
[1] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA
[2] Merck, Darmstadt, Germany
[3] Univ Penn, Dept Med, Philadelphia, PA 19104 USA
[4] Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA
[5] Nagasaki Univ, Sch Med, Dept Oncol, Nagasaki 852, Japan
关键词
anti-idiotypic antibody; cellular immunity; GD2; ganglioside; melanoma;
D O I
10.1007/s00262-002-0340-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:145 / 154
页数:10
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