Local administration of cytostatic drug 4-hydroperoxy-cyclophosphamide (4-HPCY) facilitates cell-mediated immune reactions.
4-Hydroperoxy-cyclophosphamide (4-HPCY) is a cyclophosphamide (CY) derivative that, unlike CY, does not need liver conversion for its action. This new drug has been recently described to preferentially eliminate suppressor B and T lymphocytes in vitro in both mice and man. Using an in vivo contact sensitivity model in the guinea-pig, we introduced 4-HPCY into antigenically stimulated lymph nodes by local intradermal injection following sensitization. Strong potentiation of contact sensitization was achieved by local administration of doses higher than 50 micrograms 4-HPCY daily on 4 days subsequent to sensitization. Contact hypersensitivity was found to be enhanced for at least 6 weeks. In addition it could be demonstrated that local administration of 4-HPCY not only enhanced the development of delayed hypersensitivity in normal animals, but also facilitated the reversal of previously induced immunological tolerance. The applicability of this new strategy for potentiation of effector T cell function, especially with respect to the treatment of malignancies, is stressed.
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003877:Dermatitis, Contact; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006168:Guinea Pigs; D007108:Immune Tolerance / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects*; D007271:Injections, Intradermal; D013997:Time Factors
D000276:Adjuvants, Immunologic; D003520:Cyclophosphamide; C011272:perfosfamide