Human-based Polyclonal Antibodies to Ricin

摘要

The feasibility of producing a human polyclonal antibody to ricin intoxication was demonstrated. Investigators manufactured a relatively-benign yet full-length, ricin-like toxoid according to a cGMP standard with a view to immunizing healthy volunteers (plasma donors). The immunogenic potential of the toxoid was convincingly demonstrated in GLP and non-GLP animal studies and in a parallel Phase I human clinical trial (involving cancer patients). Simultaneously the post-exposure protective benefits of polyclonal antibodies where shown in rodents which were subjected to normally lethal doses of ricin. Despite the technical success, manufacture and stockpiling of a hyperimmune human polyclonal was ultimately not possible due to safety concerns related to the administration of ricin toxoid to healthy volunteers. In the concluding phase of the project, the investigators collected human peripheral lymphocytes from consenting cancer patients who had received >6 months of treatments (weekly injections) with toxoid. Investigators are positioned to clone a high affinity anti-ricin monclonal from 'affinity-maturated' antibody-genes.