Selective Regulatory T Cell Expansion with AMG 592: A Promising IL-2 Mutein for Inflammatory Diseases

The abstract discusses the therapeutic potential of a modified interleukin-2 (IL-2) called AMG 592, which is being studied for its selective action on regulatory T cells (Tregs) over effector T cells and natural killer (NK) cells. This compound is intended to minimize toxicity associated with conventional IL-2 therapy. The research included in vitro and in vivo tests, as well as a phase 1 clinical trial.

In vitro, AMG 592 demonstrated a more selective activation of Tregs and reduced inflammatory cytokine production compared to standard IL-2. In animal models, it induced Treg expansion without significant changes in body temperature or C-reactive protein levels, unlike standard IL-2.

The phase 1 clinical trial involved healthy volunteers receiving various doses of AMG 592 or a placebo. The compound was found to be well tolerated, with the most common side effect being mild, localized skin reactions. Pharmacokinetic data showed an increase in serum levels of AMG 592 that correlated with the administered dose. It also led to a significant and sustained increase in the ratio of Tregs to conventional T cells, with the peak effect observed around day 8 post-injection.

Importantly, AMG 592 did not alter NK cell numbers or significantly increase conventional T cell counts. Furthermore, it did not elevate levels of pro-inflammatory cytokines, suggesting a safer therapeutic profile than conventional IL-2.

The conclusion of the study is that AMG 592 selectively expands Tregs in a dose-dependent manner without causing a systemic inflammatory response. This suggests that AMG 592 may offer a broader therapeutic window and potentially allow for less frequent dosing. The study advocates for further research into the use of AMG 592 in treating inflammatory and autoimmune diseases by leveraging the immune-regulating properties of Tregs.