Drug-induced alopecia is a major side of effect of anticancer therapy. Although not life-threatening, the loss of hair can be emotionally devastating for a patient and therefore lead to a refusal of further chemotherapy. Recent results demonstrate that a neutralizing murine anti- doxombicin antibody (MAD11) prevents chemotherapy-induced toxicity in mice. This MAb was shown to prevent doxorubicin-induced alopecia in rodents(Balsari et al, 1994) and in a human phase trial (Balsari unpublished). The MAb, applied topically or taken orally, did not compromise anthracycline anti-tumor activity. This laboratory has pioneered proprietary methods for the production of secretory lgA antibodies in transgenic plants (Ma et al. 1995). SlgA plantibodies are the preferred form of antibody therapy for topical, oral or enteric use. The overall goal of the present project is to prepare an SIgA form of MAD11 as an economical, stable topical adjunctive agent to reduce doxorubicin-induced alopecia. In phase I we will clone and sequence heavy and light chain variable regions of MAD11. These will be used to construct secretory IgA plantibody expression cassettes for particle bombardment- mediated transformation of alfalfa plants to produce transgenic SIgA. Finally, we will evaluate doxorubicin binding and activity of the SIgA plantibody form of MAD11. Successful completion of this project will demonstrate a general method to reduce mucosal and topical toxicity of other chemotherapeutic agents.
Construction of anti-Doxorubicin plantibodies will provide a novel therapeutic to alleviate alopecia induced by this widely used anti-cancer drug with a significant market opportunity.
