Comparative analysis of the immunopharmacological properties of three new nitrosourea analogues: RPCNU, RFCNU and Chlorozotocin.

Three sugar derivatives of chloroethyl nitrosoureas: RPCNU, RFCNU and Chlorozotocin (CLZ) were examined for their effect on the immune system in mice when administered at the minimal antineoplastic therapeutic dose. When the drugs were administered 4 days prior to antigenic stimulation, a potentiation of DTH to oxazolone was observed whereas the antibody response to SRBC was markedly decreased. When injected 24 h after immunization, the nitrosourea analogues did not modify the intensity of DTH reaction and of allograft rejection and only RFCNU depressed the antibody response. The proliferative response of spleen cells to T or B cell mitogens was strongly depressed after in vivo treatment with either of the three analogues. Concomitantly, peritoneal macrophages became strongly cytostatic for tumor cells and also displayed an enhanced chemiluminescence upon phagocytosis. An augmentation of antibody-dependent cellular cytotoxicity of spleen cells was observed only after CLZ administration which also resulted in an increase of NK activity of peritoneal cells but in an inhibition of spleen cell cytotoxicity. This study demonstrates that the nitrosourea analogues act as immunomodulating agents and reinforces their interest as antineoplastic drugs since they can stimulate nonspecific effector mechanisms known to play a role in resistance against tumors.