Details

Autor(en) / Beteiligte

• Wang, Yifei
• Tian, Xiangjun
• Zhang, Wendong
• Zhang, Zhongting
• Lazcano, Rossana
• Hingorani, Pooja
• Roth, Michael E
• Gill, Jonathan D
• Harrison, Douglas J
• Xu, Zhaohui
• Jusu, Sylvester
• Kannan, Sankaranarayanan
• Wang, Jing
• Lazar, Alexander J
• Earley, Eric J
• Erickson, Stephen W
• Gelb, Tara
• Huxley, Philip
• Lahdenranta, Johanna
• Mudd, Gemma
• Kurmasheva, Raushan T
• Houghton, Peter J
• Smith, Malcolm A
• Kolb, Edward A
• Gorlick, Richard

Titel

Comprehensive Surfaceome Profiling to Identify and Validate Novel Cell-Surface Targets in Osteosarcoma

Ist Teil von

• Molecular cancer therapeutics, 2022-06, Vol.21 (6), p.903-913

Ort / Verlag

United States

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Immunoconjugates targeting cell-surface antigens have demonstrated clinical activity to enable regulatory approval in several solid and hematologic malignancies. We hypothesize that a rigorous and comprehensive surfaceome profiling approach to identify osteosarcoma-specific cell-surface antigens can similarly enable development of effective therapeutics in this disease. Herein, we describe an integrated proteomic and transcriptomic surfaceome profiling approach to identify cell-surface proteins that are highly expressed in osteosarcoma but minimally expressed on normal tissues. Using this approach, we identified targets that are highly expressed in osteosarcoma. Three targets, MT1-MMP, CD276, and MRC2, were validated as overexpressed in osteosarcoma. Furthermore, we tested BT1769, an MT1-MMP-targeted Bicycle toxin conjugate, in osteosarcoma patient-derived xenograft models. The results showed that BT1769 had encouraging antitumor activity, high affinity for its target, and a favorable pharmacokinetic profile. This confirms the hypothesis that our approach identifies novel targets with significant therapeutic potential in osteosarcoma.