Data from: Targeted computational design of an interleukin-7 superkine with enhanced folding efficiency and immunotherapeutic efficacy

Interleukin-7 (IL-7) plays a central role in maintaining T cell
development and immune homeostasis, and enhancing the cytokine’s
immune-stimulatory functionality has broad therapeutic implications
against various oncological malignancies. Herein, we show a
computationally designed IL7 superkine, Neo-7, which exhibits enhanced
folding efficiency and superior binding affinity to its cognate receptors.
To streamline the protein candidate prediction and validation process, the
loop region of IL7 was strategically targeted for redesign while most of
the receptor-interacting regions were preserved. Leveraging advanced
computational tools such as AlphaFold2, we show loop remodeling to rectify
structural irregularities that allows for iterative stabilization of
protein backbone and leads to identification of beneficial mutations
conducive to receptor engagement. Neo-7 superkine shows improved
thermostability and production yield, and it exhibits heightened
immune-stimulatory and anticancer effect. These findings underscore the
utility of a targeted computational approach for de novo cytokine
development.