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Published on: September 16, 2019
Identification of an antilaminin-1 scFv that preferentially homes to vascular solid tumors
Sandra M Davern1, Linda J Foote, Trish K Lankford
1Oak Ridge National Laboratory, Building 45005, Bethel Valley Road, Oak Ridge, TN 37831, USA.
Abstract:
The tumor vasculature and extracellular matrix make attractive targets for distinguishing solid tumors from normal cells. In solid tumors, the processes of angiogenesis and metastasis potentially give rise to unique epitopes not usually accessible in homeostatic organs. Specific targeting of solid tumors for radioimmunotherapy requires that the targeting agent accumulate rapidly and at high levels at the tumor site. This study involved the selection of scFvs that recognize laminin-1 in vitro from the Tomlinson I and J phage display libraries. Selected, purified scFvs were radioiodinated and injected in tumor-bearing mice. One of these, scFv 15-9, exhibited preferential accumulation at subcutaneous tumors when compared to other antilaminin scFvs or to a control scFv. Autoradiographic analysis indicated that scFv15- 9 also displayed a higher vessel:parenchyma ratio than did two other antilaminin scFvs, scFv 15-6 and scFv 15-1, indicating a preferential accumulation of scFv 15-9 around vessel structures. Immunohistochemistry confirmed that scFv 15-9 accumulated at sites of endothelial cells lining vessel structures where significant levels of laminin were present. These data demonstrate that scFv 15-9 binds to a specific epitope on laminin and has potential for tumor endoradiotherapy in subcutaneous tumors.
Insights
Researchers identified a novel antibody fragment, scFv 15-9, that targets laminin-1 in solid tumors. This fragment shows potential for radioimmunotherapy by accumulating specifically in tumor vasculature.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Solid tumors present unique molecular targets in their vasculature and extracellular matrix.
- Angiogenesis and metastasis in tumors create distinct epitopes not found in normal tissues.
- Effective radioimmunotherapy requires targeting agents that rapidly accumulate in tumor sites.
Purpose of the Study:
- To select and characterize single-chain variable fragments (scFvs) that recognize laminin-1.
- To evaluate the tumor-targeting potential of selected scFvs in vivo.
- To identify a promising scFv for potential tumor endoradiotherapy.
Main Methods:
- Selection of anti-laminin-1 scFvs from phage display libraries.
- Radioiodination of purified scFvs.
- In vivo studies using tumor-bearing mice to assess scFv accumulation.
- Autoradiography and immunohistochemistry to analyze scFv distribution.
Main Results:
- scFv 15-9 demonstrated preferential accumulation in subcutaneous tumors compared to other anti-laminin scFvs and a control.
- Autoradiography revealed a higher vessel:parenchyma ratio for scFv 15-9, indicating vessel-specific targeting.
- Immunohistochemistry confirmed scFv 15-9 localization to endothelial cells expressing laminin.
Conclusions:
- scFv 15-9 specifically binds to an epitope on laminin-1.
- scFv 15-9 exhibits significant potential for targeting subcutaneous tumors.
- This scFv is a promising candidate for further development in tumor endoradiotherapy.
