Metastasis is responsible for 90% of all cancer-related deaths. However, current FDA-approved cancer treatments are focused on preventing tumor cell proliferation rather than migration, and the mechanisms driving tumor metastasis remain unclear. Recently, a synergistic signaling pathway involving the interleukin-6 (IL-6) cytokine and the IL-8 chemokine was reported to promote tumor metastasis, and the inhibition of this pathway was demonstrated to prevent cancer cell migration. Recombinant antibodies are valuable therapeutic candidates due to their ability to specifically target their ligands with high potency, and bispecific antibodies offer the additional advantages of enhanced affinity through avidity effects, improved target cell specificity, and reduced chances of secondary resistance due to mutational escape. We engineered two bispecific antibody-based constructs that simultaneously block activation of the IL-6 and IL-8 receptors, and characterized their biophysical and functional properties. We demonstrated the efficacy of our bispecific antibodies in blocking cell migration in highly aggressive cancer types, including triple negative breast cancer. Ongoing studies seek to evaluate these constructs in 3-D cellular migration studies and in mouse tumor xenograft models to advance the development of effective molecular therapeutics targeting cancer metastasis.

Engineered bispecific antibodies for targeted inhibition of cancer metastasis

2019 Spring National Meeting

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