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

Elise Solli1,2, Alessio Bevilacqua3, Mathias Wenes4,5

  • 1Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Norway.

Molecular Oncology
|January 22, 2026
PubMed
Summary

Roginolisib effectively targets leukemia cells like idelalisib but better preserves T-cell functions. This PI3K inhibitor may offer a safer alternative for hematological cancer treatment.

Keywords:
CD4+ T helper cellCD8+ cytotoxicityPI3K inhibitorT‐cell functionchronic lymphocytic leukemiaregulatory T cells

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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.