ONLINE COVER IL-2 Mutein Passes an Acid Test. This month’s cover depicts a glycolytic tumor releasing lactic acid molecules, establishing an acidic tumor microenvironment (TME). The low pH of the TME suppresses antitumor immune responses and favors tumor growth. Gaggero and Martinez-Fabregas et al. report that cytokines are extremely sensitive to the acidic pH found in tumors and lymph nodes. The activity of IL-2, a cytokine central to T cell responses, is highly limited at acidic pH. Using in vitro evolution, they identify a new IL-2 variant, Switch-2, that exhibits enhanced activity at acidic pH but, surprisingly, exhibits reduced activity at the neutral pH found in healthy tissue. Switch-2 therapy in mice triggered potent antitumor responses while avoiding the severe systemic toxicity associated with current high-dose IL-2 therapies.
Credit: Paul K. FyfeScience Immunology
- Volume 7|
- Issue 78|
- Dec 2022
ONLINE COVER IL-2 Mutein Passes an Acid Test. This month’s cover depicts a glycolytic tumor releasing lactic acid molecules, establishing an acidic tumor microenvironment (TME). The low pH of the TME suppresses antitumor immune responses and favors tumor growth. Gaggero and Martinez-Fabregas et al. report that cytokines are extremely sensitive to the acidic pH found in tumors and lymph nodes. The activity of IL-2, a cytokine central to T cell responses, is highly limited at acidic pH. Using in vitro evolution, they identify a new IL-2 variant, Switch-2, that exhibits enhanced activity at acidic pH but, surprisingly, exhibits reduced activity at the neutral pH found in healthy tissue. Switch-2 therapy in mice triggered potent antitumor responses while avoiding the severe systemic toxicity associated with current high-dose IL-2 therapies.
Credit: Paul K. Fyfe
