Specific immunosuppression by immunotoxins containing daunomycin.
Daunomycin, when conjugated with a targeting antigen by an acid-sensitive spacer, remains inactive at the intravascular pH of 7 but becomes active after cleavage within the acidic lysosomal environment of the target cell. This observation made it possible to construct cytocidal compounds that caused antigen-specific suppression of murine lymphocyte function. When daunomycin was coupled to the hapten conjugate of ovalbumin by an acid-sensitive cis-aconityl group, it caused hapten-specific impairment of immunocompetence in murine B lymphocytes in vitro and in vivo. Furthermore, the response by T lymphocytes to concanavalin A in vitro was selectively eliminated by a conjugate between daunomycin plus the acid-sensitive spacer and a monoclonal antibody specific for T cells.
D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy; D003208:Concanavalin A / Q000494:pharmacology; D003630:Daunorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D019793:Fluorescein; D005452:Fluoresceins / Q000008:administration & dosage / Q000494:pharmacology; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008808:Mice, Inbred CBA; D009592:Nitrohydroxyiodophenylacetate / Q000008:administration & dosage / Q000494:pharmacology; D010047:Ovalbumin / Q000008:administration & dosage / Q000494:pharmacology; D010851:Picrates / Q000008:administration & dosage / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects
D005452:Fluoresceins; D007166:Immunosuppressive Agents; D010851:Picrates; D003208:Concanavalin A; D009592:Nitrohydroxyiodophenylacetate; D010047:Ovalbumin; C005858:picric acid; D019793:Fluorescein; D003630:Daunorubicin