(22d) Engineered Bispecific Antibodies for Targeted Inhibition of Cancer Metastasis
AIChE Annual Meeting
2019
2019 AIChE Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Engineering in Cancer Biology and Therapy I: Research Tools and Platforms
Sunday, November 10, 2019 - 4:24pm to 4:42pm
Recently, our team discovered a new biochemical pathway involving the interleukin-6 (IL-6) cytokine and the interleukin-8 (IL-8) chemokine that actively drives tumor cell migration. We further demonstrated that blocking signaling through both the IL-6 and IL-8 receptors using an antibody/small molecule combination therapy regimen significantly decreased tumor cell migration in vitroand also markedly suppressed cancer metastasis in vivo. However, translation of this combination therapy strategy into patients is complicated by logistical challenges, such as dosing ratio optimization, as well as increased regulatory hurdles. Moreover, small molecule drugs face significant clinical challenges in terms of specificity.
To overcome the logistical and regulatory limitations associated with antibody/small molecule combination therapy, we have engineered newbispecific antibodiesthat simultaneously engage the IL-6 and IL-8 receptors (IL-6R and ILâ8R). Compared to monoclonal antibodies, bispecific antibodies exhibit enhanced affinity, potency, and selectivity while reducing risk of drug resistance by concurrently blocking two different pathways.The novel antibodies we designed have vast clinical potential for treating a range of cancer types, particularly highly aggressive neoplasias such as triple negative breast cancer and pancreatic duct adenocarcimona. We have characterized the binding and competitive properties of our engineered bispecific antibodies, and demonstrated their efficacy in blocking tumor cell migration in 3D collagen matrices and inhibiting metastasis in mouse tumor xenograft models. Overall, these results present an exciting opportunity for targeted inhibition of cancer metastasis, which can also synergize with current clinical therapies targeting tumor growth.