The augmentation of tumor-specific immunity using haptenic muramyl dipeptide (MDP) derivatives |
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Authors: | Toshiyuki Hamaoka Yasuyuki Takai Atsushi Kosugi Yumiko Mizushima Junko Shima Tsuneo Kusama Hiromi Fujiwara |
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Affiliation: | (1) Department of Oncogenesis, Institute for Cancer Research, Osaka University Medical School, 1-1-50 Fukushima, Fukushima-ku, 553 Osaka, Japan;(2) Research Institute, Daiich Seiyaku, Co., LTD., 1-16-13, Kitakasai, Edogawa-ku, 134 Tokyo, Japan |
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Abstract: | Summary A new haptenic compound, a muramyl dipeptide (MDP) derivative (designated as L4-MDP-ONB) cross-reactive with Bacillus Calmette Guerin (BCG) was synthesized. The cross-reactivity of L4-MDP hapten to BCG was demonstrated from the following evidence; (a) lymph node cells from BCG-primed C3H/HeN mice exhibited appreciable L4-MDP-specific proliferative responses to the in vitro stimulation of L4-MDP-modified syngeneic cells (L4-MDP-self); (b) inoculation of L4-MDP-self into footpads of BCG-primed C3H/HeN mice elicited ample delayed type-hypersensitivity (DTH) responses in vivo as measured by footpad swelling; and (c) BCG-primed mice contained L4-MDP-reactive helper T cell activity which functions to augment the generation of effector T cell responses to cell surface antigens. This crossreactivity between L4-MDP hapten and BCG as measured by the helper T cell activity was applied to enhanced induction of tumor-specific immunity. When BCG-primed C3H/HeN mice were immunized with L4-MDP-modified syngeneic X5563 tumor cells, these mice could generate augmented tumor-specific in vivo protective (tumor neutralizing) immunity as well as in vitro cytotoxic T cell responses. These results indicate the effectiveness of L4-MDP hapten in augmenting tumor-specific immunity. The present approach is discussed in the context of potential advantages of this new hapten for its future application to clinical tumor systems. |
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