Deborah Bradley-Dunlop

An egg-specific monoclonal antibody to Lygus hesperus

Abstract A species- and stage-specific monoclonal antibody (MAb) for a Lygus hesperus Knight egg antigen was developed. Positive antigen-antibody reactions were associated only with L. hesperus eggs and adult females. There was no cross-reactivity with any of the other L. hesperus life stages nor with any stage of L. lineolaris (Palisot de Beauvois). Furthermore, this MAb did not cross-react with the eggs of 10 other insect species examined. Electrophoretic and Western blot analyses indicated that the egg antigen had four polypeptides that bound to this MAb with molecular weights estimated at 64,000, 123,250, 140,300, and 150,300 Da. The use of this MAb as a diagnostic probe for gut content analysis of potential natural predators of L. hesperus eggs is discussed.

The vitamin E analog, alpha-tocopheryloxyacetic acid enhances the anti-tumor activity of trastuzumab against HER2/neu-expressing breast cancer

BackgroundHER2/neu is an oncogene that facilitates neoplastic transformation due to its ability to transduce growth signals in a ligand-independent manner, is over-expressed in 20-30% of human breast cancers correlating with aggressive disease and has been successfully targeted with trastuzumab (Herceptin®). Because trastuzumab alone achieves only a 15-30% response rate, it is now commonly combined with conventional chemotherapeutic drugs. While the combination of trastuzumab plus chemotherapy has greatly improved response rates and increased survival, these conventional chemotherapy drugs are frequently associated with gastrointestinal and cardiac toxicity, bone marrow and immune suppression. These drawbacks necessitate the development of new, less toxic drugs that can be combined with trastuzumab. Recently, we reported that orally administered alpha-tocopheryloxyacetic acid (α-TEA), a novel ether derivative of alpha-tocopherol, dramatically suppressed primary tumor growth and reduced the incidence of lung metastases both in a transplanted and a spontaneous mouse model of breast cancer without discernable toxicity.MethodsIn this study we examined the effect of α-TEA plus HER2/neu-specific antibody treatment on HER2/neu-expressing breast cancer cells in vitro and in a HER2/neu positive human xenograft tumor model in vivo.ResultsWe show in vitro that α-TEA plus anti-HER2/neu antibody has an increased cytotoxic effect against murine mammary tumor cells and human breast cancer cells and that the anti-tumor effect of α-TEA is independent of HER2/neu status. More importantly, in a human breast cancer xenograft model, the combination of α-TEA plus trastuzumab resulted in faster tumor regression and more tumor-free animals than trastuzumab alone.ConclusionDue to the cancer cell selectivity of α-TEA, and because α-TEA kills both HER2/neu positive and HER2/neu negative breast cancer cells, it has the potential to be effective and less toxic than existing chemotherapeutic drugs when used in combination with HER2/neu antibody.

Presence of non-Fab IgE binding molecules in the intestinal nematode parasite of mice Heligmosomoides polygyrus

Unsuccessful attempts to identify serum parasite-specific immunoglobulin E (IgE) responses in mice following infections with the intestinal nematode parasite Heligmosomoides polygyrus prompted us to explore the possibility that IgE bound within the parasite antigen could account for the false-positive results observed. A live-worm ELISA was developed. Following incubation, irrelevant IgE monoclonal antibody to DNP, IgE present in normal mouse serum, as well as IgE in immune serum were independently identified within live adult worms in this H. polygyrus-modified ELISA. It was concluded that in addition to parasite-specific IgE binding to H. polygyrus, the parasite may attract both parasite-specific and non-parasite-specific IgE via non-Fab IgE-binding molecules.