Molecular and biological properties of an abrin A chain immunotoxin designed for therapy of human small cell lung cancer.

@article{Wawrzynczak1992MolecularAB,
  title={Molecular and biological properties of an abrin A chain immunotoxin designed for therapy of human small cell lung cancer.},
  author={Edward J. Wawrzynczak and Uwe Zangemeister‐Wittke and Robert J Waibel and Raymond V. Henry and Geoffrey D. Parnell and Alan J. Cumber and M. Jones and Rolf Stahel},
  journal={British Journal of Cancer},
  year={1992},
  volume={66},
  pages={361 - 366}
}
An immunotoxin (IT) comprising abrin A chain attached to the mouse monoclonal antibody SWA11, recognising a cell surface antigen highly associated with human small cell lung cancer (SCLC), was synthesised using a hindered disulphide crosslinker, N-succinimidyl 3-(2-pyridyldithio) butyrate (SPDB), and purified by Blue Sepharose CL-6B affinity chromatography. The IT preparation contained monomeric conjugate, composed of one abrin A chain molecule linked to one SWA11 molecule, and was free from… 
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The potential of mouse monoclonal antibodies for recognising different antigens associated with human small cell lung cancer (SCLC) to form active immunotoxins was assessed by an indirect in vitro
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The A-chain of the plant toxin abrin was covalently linked to monoclonal anti-Thy 1.1 antibody (OX7) with the use of either N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) or 2-iminothiolane
Pharmacokinetics in the rat of a panel of immunotoxins made with abrin A chain, ricin A chain, gelonin, and momordin.
TLDR
Fib75-abrin A chain was found to be about 3- to 4-fold more resistant than the other immunotoxins to breakdown by reduction of the disulfide linkage between the A chain and the antibody with glutathione in vitro, which suggests that the longer serum half-life of Fib75-abs Rin A chain may have been due to greater stability against reduction in vivo.
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TLDR
These covalent conjugates, particularly the one containing abrin A-chain, may find application in freeing human bone marrow ex vivo of infiltrated tumor cells prior to reinfusion as an autograft.
Immunotoxins to a human melanoma-associated antigen: comparison of gelonin with ricin and other A chain conjugates.
TLDR
In vivo experiments showed that gelonin conjugates are not toxic up to 2 mg total dose/mouse and significantly retarded the growth of established s.c. tumor.
Comparative biochemical, cytotoxic and pharmacokinetic properties of immunotoxins made with native ricin a chain, ricin A1 chain and recombinant ricin a chain
TLDR
The β‐phase half‐lives of fib75‐recombinant ricin A chain and Fib75‐ricin A, chain were similar, consistent with the identical susceptibility of the immunotoxins to cleavage by glutathione, as well as the presence of the complex‐type oligosaccharide side‐chain on the A1 chain, which may have accelerated the clearance of the A2 chain immunotoxin.
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TLDR
Both the use of the SMPT cross-linker and deglycosylation of the A-chain significantly improve the therapeutic index of the immunotoxins in AKR-A/2 tumor-bearing mice.
Selective antitumor effect on L10 hepatocarcinoma cells of a potent immunoconjugate composed of the A chain of abrin and a monoclonal antibody to a hepatoma-associated antigen.
TLDR
In vivo studies showed that the conjugate was not toxic at a dosage of 60 to 1120 micrograms/guinea pig, the conjUGate decreased or abolished the growth of established solid tumors, the Conjugate delayed or inhibited tumor metastases to lymph nodes, and 20 to 40% of the animals in selective groups had a long-term complete regression.
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