A team of Rice University bioengineers has developed a mathematical model that clarifies why interleukin-12 (IL-12) ⎯ a potent immune-boosting protein that holds promise for cancer treatment ⎯ loses effectiveness over time when used as an immunotherapeutic. The research challenges long-held assumptions about IL-12's behavior in the body and offers a path toward safer and more effective dosing regimens. IL-12 has a lot of potential for cancer immunotherapy , but dosing it effectively has proven very difficult and a key reason why IL-12 therapies have struggled to achieve hoped-for results in clinical trials over the past 30 years.

" Oleg Igoshin, professor of bioengineering and chemistry and associate chair of the Department of Bioengineering, Rice University IL-12 belongs to a class of proteins known as cytokines that immune cells use to communicate with each other to coordinate the body's defenses against antigens. In theory, IL-12 could be used to help the body recognize cancer cells as harmful and boost the immune system's capacity to target and break down tumors. In practice, however, not only do blood IL-12 levels decrease over time despite steady dosage, but also the strength of the IL-12-induced immune response is gradually dampened.

This phenomenon is known as desensitization. "Understanding IL-12 desensitization is essential for figuring out how to develop a successful IL-12-based immunotherapy," said Jonathon DeBonis, a Rice Ph.D.

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