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.
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.
Hamaoka
T
T
Takai
Y
Y
Kosugi
A
A
Mizushima
Y
Y
Shima
J
J
Kusama
T
T
Fujiwara
H
H
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000276:immunology; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D003429:Cross Reactions; D005260:Female; D006241:Haptens; D006968:Hypersensitivity, Delayed; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D001500:BCG Vaccine; D006241:Haptens; D000119:Acetylmuramyl-Alanyl-Isoglutamine