Comprehensive Surfaceome Profiling to Identify and Validate Novel Cell-Surface Targets in Osteosarcoma
Open accessPublished version of a preprint
Abstract
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.
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The intratumour and intertumour heterogeneity of osteosarcomas is substantial.
“given the intratumour and intertumour heterogeneity of osteosarcomas 186 .”
From Osteosarcoma (2022) · cites this paper as [186]
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References 44 · Cited by 37
Research works printed but not linked: 1
- [37]Biswas S, Rankin K, Long A, Nisar S, Gerrand C, Dildey P,. Abstract 5580: membrane-type 1 matrix metalloproteinase (MT1-MMP): a predictive biomarker of chemotherapy response in osteosarcoma. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012; 72 (8 Suppl): Abstract nr 5580. doi:1538-7445.AM2012-5580.
- Authors
- Wang, Y., Tian, X., Zhang, W., Zhang, Z., Lazcano, R., Hingorani, P., Roth, M. E., Gill, J. D., Harrison, D. J., Xu, Z., Jusu, S., Kannan, S., Wang, J., Lazar, A. J., Earley, E. J., Erickson, S. W., Gelb, T., Huxley, P., Lahdenranta, J., Mudd, G., Kurmasheva, R. T., Houghton, P. J., Smith, M. A., Kolb, E. A., & Gorlick, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- 1Department of Pediatrics, Children's Cancer Hospital, The University of Texas MD Anderson Cancer Center, Houston, Texas.
- RTI International (US)
- 5Bicycle Therapeutics, Lexington, Massachusetts.
- Bicycle Therapeutics (United Kingdom) (GB)
- The University of Texas at San Antonio Health Science Center (US)
- National Cancer Institute (US)
- Alfred I. duPont Hospital for Children (US)
- Corresponding author
- Gorlick, Richard
- ORCID
- Wang, Yifei
- Tian, Xiangjun
- 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
- Lahdenranta, Johanna
- Mudd, Gemma
- Kurmasheva, Raushan T.
- Houghton, Peter J.
- Smith, Malcolm A.
- Kolb, Edward A.
- Gorlick, Richard
- Venue
- Molecular Cancer Therapeutics
- Published
- 2022-03-21
- Volume
- 21
- Issue
- 6
- Pages
- 903-913
- ISSN
- 1535-7163 (ISSN-L)
- 1538-8514
- PMC
- PMC9167717
- OpenAlex
- W4220844511
- Cited by
- 37
- References
- 44
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 8 · 2023: 8 · 2022: 5
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cancer Therapeutics (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- NIH NCI (5U01CA199221–06, P30CA16672)
- NCI Cancer Center (P30CA016672)
- NIH (1S10OD012304–01)
- Cancer Prevention and Research Institute of Texas Core Facility (RP130397)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- osteosarcoma, cell surface antigens, cell surface targets, MT1-MMP, B7-H3, MRC2, immunoconjugates, patient-derived xenografts, proteomics, transcriptomics, targeted therapy
- MeSH terms
- Antigens, Surface, Bone Neoplasms, Humans, Osteosarcoma, Proteomics, Cell Line, Tumor, Matrix Metalloproteinase 14, B7 Antigens
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