In vitro and in vivo properties of an anti-CD5-momordin immunotoxin on normal and neoplastic T lymphocytes.
An anti-CD5 monoclonal antibody (mAb) was linked to the plant toxin momordin, a type-1 ribosome-inactivating protein purified from Momordica charantia. The in vitro cytotoxicity of the immunotoxin was evaluated as the inhibition of protein and/or DNA synthesis on isolated peripheral blood mononuclear cells (PBMC) and on human T cell leukemia Jurkat. The potency of the immunotoxin on PBMC was very high (IC50 = 1 - 10 pM) and was not affected by blood components. The conjugate was also very efficient in the inhibition of the proliferative response in a mixed lymphocyte reaction (IC50 = 10 pM). Moreover, the in vitro performance of the immunotoxin compared favorably with those reported for other anti-CD5-based immunoconjugates containing ricin A chain. The in vivo activity of the immunotoxin was assessed in the model of nu/nu mice bearing Jurkat leukemia. A significant inhibition of the tumour development (80%, P < 0.01) in the animals treated with immunotoxin was observed. Taken together, the in vitro and in vivo results suggest that the anti-CD5-momordin conjugate may be useful for graft-versus-host disease therapy and potentially in the treatment of CD5-positive leukemias and lymphomas.
Porro
G
G
Italfarmaco Research Centre, (Mi), Italy.
Bolognesi
A
A
Caretto
P
P
Gromo
G
G
Lento
P
P
Mistza
G
G
Sciumbata
T
T
Stirpe
F
F
Modena
D
D
D000818:Animals; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology*; D018956:CD5 Antigens; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000633:toxicity*; D015458:Leukemia, T-Cell / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009699:N-Glycosyl Hydrolases; D009368:Neoplasm Transplantation; D010940:Plant Proteins / Q000008:administration & dosage*; D014176:Protein Biosynthesis; D054790:Ribosome Inactivating Proteins, Type 2; D013601:T-Lymphocytes / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018956:CD5 Antigens; D000922:Immunotoxins; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; C470296:momordin I (protein); D004247:DNA; D009699:N-Glycosyl Hydrolases