A comparison of anti-lymphocyte immunotoxins containing different ribosome-inactivating proteins and antibodies.
Immunotoxins were prepared with several single-chain ribosome-inactivating proteins (RIPs type 1) and with the A-chain of ricin linked to the F(ab')2 fragment of sheep anti-mouse IgG. The cytotoxic activity of these conjugates was tested on human lymphocytes pretreated with an anti-CD3 murine MoAb. The immunotoxins inhibited DNA synthesis in phytohaemagglutinin (PHA)-stimulated lymphocytes with IC50S (concentrations causing 50% inhibition) ranging from 8.9 x 10(-13) to 5.7 x 10(-11) M (immunotoxins containing dianthin 32, saporin, pokeweed antiviral protein from seeds (PAP-S), bryodin, momordin, momorcochin, and trichokirin), 1 x 10(-8) M (immunotoxin containing gelonin) and 5 x 10(-9) M (immunotoxin containing ricin A-chain). The immunotoxin containing saporin linked to the anti-mouse IgG F(ab')2 fragment was also highly toxic to human lymphocytes pretreated with anti-CD2, -CD3, -CD5 and -CD45 MoAbs, with IC50S less than or equal to 10(-11) M. Immunotoxins were prepared also with saporin linked to MoAbs against various CD antigens. The immunotoxin prepared with the anti-CD3 antibody had the highest specific cytotoxicity to human lymphocytes.
Bolognesi
A
A
Dipartimento di Patologia Sperimentale, Università di Bologna, Italy.
Tazzari
P L
PL
Tassi
C
C
Gromo
G
G
Gobbi
M
M
Stirpe
F
F
D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000972:Antineoplastic Agents, Phytogenic / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D000922:Immunotoxins / Q000276:immunology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000276:immunology; D012269:Ribosomal Proteins / Q000276:immunology*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D015978:Trichosanthin / Q000276:immunology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D007074:Immunoglobulin G; D000922:Immunotoxins; D010940:Plant Proteins; D012269:Ribosomal Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D015978:Trichosanthin; D009699:N-Glycosyl Hydrolases; D000076985:Saporins