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Stability and Dependability in Cell Manufacturing: The Development of an AI-Modified IL-2 Heat Stable Agonist Protein

Application Notes

To help address some of the practical challenges of using cytokines in cell therapy manufacturing processes, we have developed an IL-2 Heat Stable Agonist Protein using artificial intelligence (AI)/predictive analytics. This thermal stable IL-2 protein contains a stabilized synthetic core and engages only the IL-2 dimeric βγ receptor complex. By evaluating the performance of this protein relative to the standard IL-2 protein under various conditions including temperature, media concentrations, and T cell outgrowth, we found that the IL-2 Heat Stable Agonist Protein performs equivalent or better than the commonly used IL-2 protein under all conditions tested. The IL-2 Heat Stable Agonist protein has a higher melting temperature (Tm), retains activity at all tested concentrations at both 37 °C and 95 °C, and performs similarly to the standard IL-2 protein in a T cell outgrowth assay. As a result, this breakthrough offers the opportunity for improved stability and dependability in the manufacture of immune-based therapies.

Key Takeaways:

  • The IL-2 Heat Stable Agonist Protein was engineered to engage only the IL-2 dimeric βγ receptor complex, making it an excellent choice for culturing T cells or tumor-infiltrating lymphocytes (TILs).
  • The melting temperature (Tm) of the IL-2 Heat Stable Agonist Protein is much higher than that of the standard IL-2 protein, and it retains activity at both 37 °C and 95 °C. 
  • The IL-2 Heat Stable Agonist Protein has enhanced stability in media over extended culture durations, allowing greater consistency throughout the production process.
  • The IL-2 Heat Stable Agonist Protein and the standard IL-2 protein promote comparable CD8⁺/CD4⁺ T cell outgrowth, with similar T cell phenotypes.

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First page of the application note describing the development and subsequent testing of the IL-2 Heat Stable Agonist Protein