Optimization of specific Frizzled Receptor-targeted antibodies signalling responses - Year two
Therapeutic antibodies have been developed against a variety cancer cell surface proteins. These antibodies activate immune surveillance mechanisms that lead to destruction of cancer cells. Therapeutic antibody efficacy can be enhanced or might have unforeseen detrimental effects due to activation or inhibition of intracellular signaling pathways. Recent evidence suggests that the targeting of subtypes of the developmentally important Frizzed receptor subtypes could have great therapeutic efficacy in the treatment of several cancers and developmental disorders. AntlerA has developed 56 agonistic antibodies against specific FZD receptors. The Michnick lab developed a series of 196 cellular pathway-specific reporter assays with which we can simultaneous monitor all known signaling pathways in any cell of interest. These assays have been applied to screen a variety of compounds and environmental toxins and results have been shown to accurately predict specificity and unpredicted additional effects that cannot be revealed by other methods. We will screen AntlerA's lead candidate recombinant antibodies for FZD receptor subtype and provide AntlerA with profiles of signaling responses, which will allow them to make decisions about which candidates would likely have the most favorable therapeutic potential and least likely unintended effects.