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Bempegaldesleukin ( BEMPEG ; NKTR ‐214) efficacy as a single agent and in combination with checkpoint‐inhibitor therapy in mouse models of osteosarcoma
Author(s) -
Hennessy Marlene,
Wahba Andrew,
Felix Kumar,
Cabrera Mariella,
Segura Maria Gabriela,
Kundra Vikas,
Ravoori Murali K.,
Stewart John,
Kleinerman Eugenie S.,
Jensen Vanessa Behrana,
Gopalakrishnan Vidya,
Pena Rhoneil,
Quach Phi,
Kim Grace,
Kivimäe Saul,
Madakamutil Loui,
Overwijk Willem W.,
Zalevsky Jonathan,
Gordon Nancy
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33382
Subject(s) - osteosarcoma , cancer research , medicine , cytotoxic t cell , immune checkpoint , immunotherapy , immunology , immune system , biology , in vitro , biochemistry
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.