Immunotoxins containing saporin 6 and monoclonal antibodies recognizing plasma cell-associated antigens: effects on target cells and on normal myeloid precursors (CFU-GM).
Monoclonal antibodies 8A and 62B1, recognizing plasma cell-associated antigens, were covalently linked to saporin 6, a ribosome-inactivating protein similar to the A-chain of ricin. Both immunotoxins were tested on target human cell lines U266 and Raji, on non-target K562 cell line and on myeloid CFU-GM progenitors. The cloning efficiency and viability of target cells were strongly reduced by 8A-saporin 6 and 62B1-saporin 6 immunotoxins, with an ID50 up to 200,000-fold lower than free saporin 6, whilst the K562 non-target cell line was unaffected. Normal human myeloid precursors (CFU-GM) were inhibited by immunotoxins only to a limited extent. An application of this model for autologous bone marrow transplantation in multiple myeloma patients is proposed. Since no eradication of cloning target cells was achieved by a single immunotoxin, mixtures made with different antibodies could help to reach this goal.
Barbieri
L
L
Dipartimento di Patologia Sperimentale, Bologna University, Italy.
Dinota
A
A
Gobbi
M
M
Tazzari
P L
PL
Rizzi
S
S
Bontadini
A
A
Lemoli
R M
RM
Tura
S
S
Stirpe
F
F
D000818:Animals; D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007074:Immunoglobulin G; D000922:Immunotoxins / Q000494:pharmacology*; D051379:Mice; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D000972:Antineoplastic Agents, Phytogenic; D007074:Immunoglobulin G; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins