Biological-based Assay for the Screening of Neutralizing Antibodies to Toxins

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Authors
  1. Furukawa-Stoffer, T.L.
  2. Weselake, R.J.
  3. Mah, M.
  4. Mah, D.
Corporate Authors
Defence Research Establishment Suffield, Ralston ALTA (CAN);Canada West Biosciences, Calgary ALTA (CAN);Lethbridge Univ, Lethbridge ALTA (CAN)
Abstract
Three mouse monoclonal hybridoma clones (designated HRF4, HHRD7 and HHRD9), were identified by their resistance to the cytotoxic effects of ricin when cultured in the presence of ricin. All were found to produce neutralizing antibody to ricin toxin. Theses hydridoma clones were selected and identified from monoclonal hybridomas obtained by cell fusion of mycloma cells and splenomic lymphocytes from ricin-hyperimmunized mice. To varying degrees, these monoclonal antibodies were able to protect myeloma cells challenged with ricin in tissue culture as well as mice challenged with co-injections of ricin. Results from this work suggests that in the preparation of neutralizing monoclonal antibodies to a cytotoxic antigen, selection using the toxin itself is an effective technique for obtaining toxin-neutralizing monoclonal antibodies. In cases where the cytotoxins are not effective against the monoclonal hybridoma cells themselves, a susceptible "indicator" cell line may be co-cultured with the monoclonal hybridomas during the selection process.
Keywords
Ricin Toxin;Binding sites;Cytotoxicity;Cancer treatments;Immunotoxins
Report Number
DRES-CR-1999-141 — Contractor Report (Final)
Date of publication
01 Mar 1999
Number of Pages
35
DSTKIM No
CA000107
CANDIS No
512216
Format(s):
Hardcopy;Document Image stored on Optical Disk

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