The PI3Kδ inhibitor roginolisib (IOA-244) preserves T-cell function and activity

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Phosphoinositide 3-kinase inhibitors (PI3Ki) show promise in hematological cancers.
• Serious immune-related adverse effects limit current PI3Ki development.
• Novel PI3Ki with improved safety profiles are needed.

Purpose of the Study:

• Evaluate the in vitro effects of roginolisib (IOA-244) and idelalisib on immune and leukemic cells.
• Compare the efficacy and safety profiles of these two PI3K inhibitors.
• Identify potential alternatives to current PI3Ki with reduced immunotoxicity.

Main Methods:

• In vitro assessment of roginolisib and idelalisib.
• Evaluation of effects on chronic lymphocytic leukemia cells.
• Analysis of T-cell signaling, activation, proliferation, and cytotoxic function.

Main Results:

• Both roginolisib and idelalisib inhibited leukemic cell signaling and viability.
• Both drugs demonstrated on-target PI3K inhibition in T cells.
• Roginolisib preserved T-cell functions, including cytotoxic activity and differentiation, unlike idelalisib.
• Idelalisib showed greater potency in reducing regulatory T-cell frequency but impaired CD8+ T-cell function.

Conclusions:

• Roginolisib is an effective PI3K inhibitor for leukemic cells.
• Roginolisib preserves critical T-cell functions, unlike idelalisib.
• Roginolisib represents a promising alternative PI3K inhibitor with a potentially improved safety profile for hematological cancers.