Neuronotoxic effects of monoclonal anti-Thy 1 antibody (OX7) coupled to the ribosome inactivating protein, saporin, as studied by suicide transport experiments in the rat.
As a first attempt to develop suicide transport agents based upon antineuronal antibodies, we studied an immunotoxin directed against the Thy 1 antigen which is on rat neurons. The immunotoxin was composed of mouse monoclonal anti-Thy 1 antibody (OX7) and the ribosome-inactivating protein, saporin, and was prepared using the heterobifunctional cross linker, SPDP, which provides a disulfide linkage between the two protein components. This immunotoxin reliably and selectively destroyed ipsilateral vagal motor and sensory neurons after injection into the cervical vagus. Injection of the immunotoxin into the caudate nucleus produced destruction of the ipsilateral substantia nigra, pars compacta and intralaminar thalamic nuclei (parafascicular and central median). Anti-mouse IgG immunoperoxidase staining confirmed axonal transport of OX7 by vagal sensory and motor neurons and by caudate afferents and efferents. Systemic toxicity was not observed with OX7-saporin. The neuronotoxic effects of OX7-saporin were specific since injections of a similarly constructed immunotoxin of irrelevant specificity or a mixture of OX7 and saporin were without suicide transport activity. These results show the feasibility of using immunotoxins as suicide transport agents.
Wiley
R G
RG
Department of Neurology, Vanderbilt University, Nashville, TN.
Stirpe
F
F
Thorpe
P
P
Oeltmann
T N
TN
D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology*; D002421:Caudate Nucleus / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D000922:Immunotoxins / Q000494:pharmacology*; D008297:Male; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D018800:Thy-1 Antigens; D014630:Vagus Nerve / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D018800:Thy-1 Antigens; D009699:N-Glycosyl Hydrolases; D000076985:Saporins