Immunotoxins containing saporin linked to different CD2 monoclonal antibodies: in vitro evaluation.
In this study we describe immunotoxins prepared with different CD2 monoclonal antibodies (mAbs) and a ribosome-inactivating protein, saporin. The CD2 immunotoxins were tested on different models. Anti-CD2-saporin conjugates inhibited protein synthesis by a neoplastic CD2+ cell line (SKW-3) and by an interleukin 2 dependent polyclonal CD2+ lymphoid cell culture (T lymphoblasts), with IC50s ranging from 10(-13) M to 10(-11) M (as saporin). Similar results were obtained with proliferation inhibition tests (3H-thymidine incorporation) on phytohaemagglutinin (PHA) driven lymphoid cultures and on mixed lymphocyte culture activated lymphocytes. Moreover a CD2-ricin A chain conjugate was less effective than an analogous immunotoxin containing the same CD2 mAb and saporin in inhibiting lymphocyte proliferation induced by PHA (IC50 approximately 10(-9) M as ricin A chain versus 10(-12) M as saporin). The conjugates were not toxic on bone marrow stem cells. These results suggest that CD2-saporin immunotoxins could represent an effective tool for CD2+ lymphomas or leukaemias, and for T-dependent immune disorders, such as transplanted organ rejection and graft-versus-host disease.
Tazzari
P L
PL
Servizio di Immunoematologia e Trasfusionale, Policlinico S. Orsola, Bologna, Italy.
Bolognesi
A
A
De Totero
D
D
Lemoli
R M
RM
Fortuna
A
A
Conte
R
R
Crumpton
M J
MJ
Stirpe
F
F
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018801:CD2 Antigens; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D009699:N-Glycosyl Hydrolases; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000187:drug effects*; D010940:Plant Proteins / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000032:analysis / Q000276:immunology; D054789:Ribosome Inactivating Proteins, Type 1; D012276:Ricin / Q000494:pharmacology; D000076985:Saporins; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D000972:Antineoplastic Agents, Phytogenic; D018801:CD2 Antigens; D000922:Immunotoxins; D009363:Neoplasm Proteins; D010940:Plant Proteins; D011971:Receptors, Immunologic; D054789:Ribosome Inactivating Proteins, Type 1; D012276:Ricin; D009699:N-Glycosyl Hydrolases; D000076985:Saporins