Suppression of antibody responses to ricin A chain (RTA) by monoclonal anti-RTA antibodies.
Balb/c mice treated with an immunotoxin constructed by conjugation of murine monoclonal antibody 791T/36 via a disulfide linker to ricin A chain generate a pronounced antibody response to peptide epitopes on ricin A chain. Monoclonal anti-RTA antibodies which recognize peptide epitopes have been developed and these have been used to down-regulate anti-RTA antibody responses in 791T/36-RTA immunotoxin-treated Balb/c mice. Of the five MAB tests, two (608/7 and 596/134) proved most effective, inhibiting anti-RTA antibody formation by up to 73%. MAB treatment was effective when initiated up to 3 days after immunotoxin treatment. Pharmacokinetic studies with 791T/36-RTA have shown that the immunotoxin is rapidly eliminated from the circulation, with no more than 4% remaining in blood after 24 hr. It is proposed that the down-regulation of anti-RTA antibodies is effected by MAB interfering with antigen processing.
Byers
V S
VS
Cancer Research Campaign Laboratories, University of Nottingham, UK.
Austin
E B
EB
Clegg
J A
JA
Denton
G
G
Gunn
B
B
Hooi
D
D
Hudecz
F
F
Price
M R
MR
Baldwin
R W
RW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000917:Antibody Formation; D001667:Binding, Competitive / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation; D000939:Epitopes / Q000276:immunology; D005260:Female; D007165:Immunosuppression Therapy; D000922:Immunotoxins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012276:Ricin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D000922:Immunotoxins; D012276:Ricin