Bempegaldesleukin (BEMPEG; NKTR-214) efficacy as a single agent and in combination with checkpoint-inhibitor therapy in mouse models of osteosarcoma

Marlene Hennessy, Andrew Wahba, Kumar Felix, Mariella Cabrera, Maria Gabriela Segura, Vikas Kundra, Murali K. Ravoori, John Stewart, Eugenie S. Kleinerman, Vanessa Behrana Jensen, Vidya Gopalakrishnan, Rhoneil Pena, Phi Quach, Grace Kim, Saul Kivimäe, Loui Madakamutil, Willem W. Overwijk, Jonathan Zalevsky, Nancy Gordon

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Survival of patients with relapsed/refractory osteosarcoma has not improved in the last 30 years. Several immunotherapeutic approaches have shown benefit in murine osteosarcoma models, including the anti-programmed death-1 (anti-PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) immune checkpoint inhibitors. Treatment with the T-cell growth factor interleukin-2 (IL-2) has shown some clinical benefit but has limitations due to poor tolerability. Therefore, we evaluated the efficacy of bempegaldesleukin (BEMPEG; NKTR-214), a first-in-class CD122-preferential IL-2 pathway agonist, alone and in combination with anti-PD-1 or anti-CTLA-4 immune checkpoint inhibitors in metastatic and orthotopic murine models of osteosarcoma. Treatment with BEMPEG delayed tumor growth and increased overall survival of mice with K7M2-WT osteosarcoma pulmonary metastases. BEMPEG also inhibited primary tumor growth and metastatic relapse in lungs and bone in the K7M3 orthotopic osteosarcoma mouse model. In addition, it enhanced therapeutic activity of anti-CTLA-4 and anti-PD-1 checkpoint blockade in the DLM8 subcutaneous murine osteosarcoma model. Finally, BEMPEG strongly increased accumulation of intratumoral effector T cells and natural killer cells, but not T-regulatory cells, resulting in improved effector:inhibitory cell ratios. Collectively, these data in multiple murine models of osteosarcoma provide a path toward clinical evaluation of BEMPEG-based regimens in human osteosarcoma.

Original languageEnglish (US)
Pages (from-to)1928-1937
Number of pages10
JournalInternational journal of cancer
Volume148
Issue number8
DOIs
StatePublished - Apr 15 2021

Keywords

  • IL-2 receptor agonist
  • NKTR-214
  • bempegaldesleukin
  • checkpoint inhibitors
  • osteosarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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