Novel chimeric anti-ricin antibody C4C13 with neutralizing activity against ricin toxicity

Abstract

So far, no specific therapeutic agent is available for the treatment of ricin intoxication. Here, V(H) and V(L) genes were cloned from a hybridoma cell line secreting anti-ricin mAb 4C13, which could neutralize the toxicity of ricin. A chimeric antibody, c4C13, containing 4C13 mAb variable region genes fused to human constant region genes (gamma 1, kappa), was constructed. C4C13 retained the binding activity and recognized the same, or a closely related, epitope as the original mouse antibody. Furthermore, c4C13 blocked ricin-induced cytotoxicity to SP2/0 cells. Compared with its parental mouse antibody, c4C13 will be safer when used in human body to reverse clinical ricin intoxication.

Ricinus communis Intoxications in Human and Veterinary Medicine—A Summary of Real Cases

“…Once ricin has been internalized into the cells, it cannot be inactivated by antibodies, limiting the therapeutic window. In order to circumvent the side effects of animal antisera (anaphylaxis, serum sickness), recent research focused on humanized monoclonal antibodies or recombinant antibodies [325,326]. …”

Antibody treatment against pulmonary exposure to abrin confers significantly higher levels of protection than treatment against ricin intoxication

“…Some studies however, have been carried out to evaluate the potency and timeframe for anti-ricin antibody-based passive immunization following exposure of experimental animals to lethal doses of ricin (Maddaloni et al, 2004;Wang et al, 2006Wang et al, , 2007Prigent et al, 2011). Recently, we evaluated the efficiency of postexposure treatment of pulmonary ricinosis by polyclonal antiricin antibodies, and demonstrated that survival rates can be increased by combining the antidotal treatment with the antiinflammatory compound, doxycycline (Gal et al, 2014).…”

Sub-Domains of Ricin’s B Subunit as Targets of Toxin Neutralizing and Non-Neutralizing Monoclonal Antibodies

“…Numerous groups, including ours, have reported that immunization of mice with RTB elicits a mixture of ricin toxin neutralizing and non-neutralizing antibodies ( Table S1 ) [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32]. In an effort to identify the regions (or sub-domains) of RTB that are important in eliciting protective immunity to ricin, we recently produced and characterized a collection of two neutralizing and four non-neutralizing RTB-specific murine monoclonal antibodies (mAbs) ( Fig.…”