INBRX-106: a hexavalent OX40 agonist that drives superior antitumor responses via optimized receptor clustering
Our data establish hexavalent INBRX-106 as a differentiated and more potent OX40 agonist, showcasing its ability to overcome the limitations of conventional bivalent therapies by inducing superior receptor clustering and multimeric engagement. This unique clustering mechanism amplifies OX40 signaling, driving robust T-cell activation, proliferation, and effector function in preclinical and clinical settings. These findings highlight the therapeutic potential of INBRX-106 and its capacity to redefine OX40-targeted immunotherapy, providing a compelling rationale for its further clinical development in combination with checkpoint inhibitors.
Authors
- Melissa J. Kasiewicz
- William L. Redmond (ORCID: https://orcid.org/0000-0002-2572-1731)
- Rashi Yadav
- Bryan R. Becklund
- Annah S. Rolig (ORCID: https://orcid.org/0000-0001-7080-4352)
- Yaiza Diaz De Durana
- Brendan P. Eckelman (ORCID: https://orcid.org/0009-0006-7090-2642)
- Anya Polovina
- Nisha Holay (ORCID: https://orcid.org/0000-0003-4363-3521)
- Noah D. Simons (ORCID: https://orcid.org/0000-0002-9703-5802)
- Sae Jeong Ahn
- Yoshinobu Koguchi (ORCID: https://orcid.org/0000-0002-5733-5755)
- Thi Staebler
Institutions
- Oregon Health & Science University (US)
- Providence Portland Medical Center (US)
- Mandala Biosciences (United States) (US)
- Inhibrx (United States) (US)
- The Ohio State University (US)
Publication Details
- Journal
- Journal for ImmunoTherapy of Cancer
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1136/jitc-2025-011524
- Citations
- 8
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 8.36
Funders
- M.J. Murdock Charitable Trust
- NIH Office of the Director