In an article in PNAS HPA related researchers have used a combinatorial protein library to select binders against the overexpressed cancer receptor EGFR. The design of the scaffold protein allows for selection of both calcium -and pH dependency, an approach that can generate fine-tuned binders and possibly enable new treatment regimes.

Overexpression of receptors promoting cell proliferation is a hallmark of cancer and using engineering strategies for conditional targeting of these receptors to minimize damage to healthy tissues is a feasible strategy for cancer therapy.

The conditional high-affinity binders in the CaRA (calcium-regulated affinity) library are designed to exploit the change in calcium concentration between endosomes and circulation to facilitate the specific delivery of a conjugated toxic payload to the lysosomes, independent of the trafficking of the cancer receptor itself.

In this article the authors describe the selection, engineering and characterization of CaRA binders targeting EGFR. The binders are also shown to have the expected conditional target affinity for EGFR-expressing cancer cells, which further underscore the promising therapeutic potential of CaRA binders.

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