The long standing “immune surveillance” hypothesis (which states that clinically relevant cancer represents a failure of the immune system to kill aberrant cells) has waxed and waned in popularity over the past several decades. With modern sensitive methods for detecting antibodies to tumor associated antigens, it is clear that such antibodies do exist. The antigens are often closely related to normal self antigens, arising from mutation or from expression of fetal variants of the adult protein. The modern version of the hypotheis is that these antibodies are not present in sufficient quantity nor with sufficient potency to prevent cancer progression, perhaps reflecting normal controls aimed at avoiding auto-immune disease. Therapeutically useful antibodies are thus likely to be rare within the human immune repertoire. Trellis has initiated an academic collaboration to explore the potential for discovery of anti-cancer antibodies from human cancer patients, with a focus on a particular antigen for which antibodies have been previously reported. By cloning a suite of antibodies to this antigen, we hope to identify which epitope is most significant for disease pathology.
In a separate effort, Trellis is exploring in animal models the utility of a CellSpot derived antibody against Her3. This protein, a member of the Epithelial Growth Factor family, has been implicated in cancer and several antibodies against it are in development, in the hope of extending the successful antibody treatments for cancer targeting the related Her1 and Her2 proteins. The novel aspect of the Trellis antibody is that it binds with a substantial preference to Her3 following the conformational change in Her3 induced by the growth factor Heregulin. The Trellis antibody binds to a site distant from the Heregulin binding site, and apparently acts to prevent dimerization of Her3 with Her2, an event that promotes tumor growth. By selectively targeting the activated form of Her3, efficacy should be enhanced and toxicity reduced.