An immunotoxin containing a rat IgM monoclonal antibody (Campath 1) and saporin 6: effect on T lymphocytes and hemopoietic cells.
The elimination of the cells responsible for graft-versus-host disease in allogeneic bone marrow transplantation has been attempted with a variety of methods, including the use of the ribosome-inactivating toxin ricin bound to monoclonal antibodies acting as carriers. However the high nonspecific toxicity of these immunotoxins containing the whole toxin greatly limited clinical application. Toxicity can be reduced using the A-chain of ricin or other ribosome-inactivating proteins (RIPs) which are devoid of a B-chain with lectin properties. We used saporin 6 purified from Saponaria officinalis seeds, which was conjugated with the rat IgM monoclonal antibody Campath 1 specific for mature T and B lymphocytes as well as for monocytes. The immunotoxin retained both RIP and antibody activity, inhibiting protein synthesis both in a cell-free system and in cells bearing the Campath 1 antigen; it also abolished methyl 3H-thymidine uptake in phytohemagglutinin-stimulated T lymphocytes. Myeloid progenitors were largely spared as shown by myeloid stem cell (CFU-GM) growth which was scarcely affected. Toxicity of the immunotoxin to cell lines not expressing the antigen recognized by Campath 1 monoclonal antibody was not greater than the toxicity due to free saporin 6, while the immunotoxin was more toxic to mice than free saporin.
Tazzari
P L
PL
Istituto di Ematologia L.&A. Seragnoli, Bologna, Italy.
Barbieri
L
L
Gobbi
M
M
Dinota
A
A
Rizzi
S
S
Bontadini
A
A
Pession
A
A
Tura
S
S
Stirpe
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D002460:Cell Line; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007075:Immunoglobulin M; D000922:Immunotoxins / Q000633:toxicity*; D007928:Lethal Dose 50; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000633:toxicity*; D011500:Protein Synthesis Inhibitors / Q000633:toxicity*; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D000922:Immunotoxins; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins