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The augmentation of tumor-specific immunity using haptenic muramyl dipeptide (MDP) derivatives

I. Synthesis of a novel haptenic MDP derivative cross-reactive with Bacillus Calmette Guerin and its application to enhanced induction of tumor immunity

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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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Hamaoka, T., Takai, Y., Kosugi, A. et al. The augmentation of tumor-specific immunity using haptenic muramyl dipeptide (MDP) derivatives. Cancer Immunol Immunother 20, 183–188 (1985). https://doi.org/10.1007/BF00205573

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Keywords

  • Lymph Node
  • Cell Activity
  • Cell Response
  • Surface Antigen
  • Dipeptide