The immunological activity of plant toxins used in the preparation of immunotoxins--II. The immunodepressive activity of gelonin.
The immunological activity of Gelonin, a 30,000 dalton plant protein possessing close similarity to Ricin chain A as a protein synthesis inhibitor which may be of interest for the preparation of antibody-toxin conjugates, was studied in mice. At in vitro concentrations not affecting baseline radioactivity uptake, this substance reduced mitogen responses with the following order of sensitivity PHA less than ConA less than LPS. In microgram/ml concentrations it also markedly reduced macrophage-dependent cytotoxicity while not affecting NK activity. Macrophagic (but not NK) cytotoxicity and mitogen responses were similarly depressed after in vivo treatment. When given before (but not after) stimulus, Gelonin also reduced the primary responses to a T-dependent and, although to a lower degree, to a T-independent antigen, and decreased resistance to allogeneic tumor grafts and L. monocytogenes challenges. The immunopharmacological activity of this and similar substances should be considered in the design of antibody-toxin conjugates and in the evaluation of their therapeutic activity.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects; D007166:Immunosuppressive Agents; D007694:Killer Cells, Natural / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy; D008088:Listeriosis / Q000188:drug therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010940:Plant Proteins / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1; D013154:Spleen / Q000166:cytology; D014118:Toxins, Biological / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D014118:Toxins, Biological; C025674:GEL protein, Gelonium multiflorum