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J Nucl Med. 2008; 49 (Supplement 1):319P
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Oncology-Basic Science: Basic Science

Basic Science Posters

Novel nanomolecular HLA-DR10 antibody mimics provide a potent system for molecular therapy and imaging

Gerald DeNardo1, Arutselvan Natarajan1, Saphon Hok2, Gary Mirick1, Sally DeNardo1, Michele Corzett2, Vladimir Sysko1, Joerg Lehmann1, Laurel Beckett3 and Rod Balhorn2

1 Internal Medicine, UC Davis, Sacramento, California; 2 Lawrence Livermore Nat'l Laboratories, Livermore, California; 3 Public Health Sciences, UC Davis, Davis, California

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Objectives: To mimic Ab behavior while decreasing size, nanomolecules (SHALs) have been created that bind to defined sites on HLA-DR10, a protein upregulated on malignant B-lymphocytes.

Methods: A lysine-polyethyleneglycol backbone was used to link ligands to generate a series of SHALs with a biotin or DOTA attached to the linker. Using binding and cell death assays, and confocal microscopy, SHAL fate and effects in HLA-DR10 expressing and non-expressing cells were assessed.

Results: All of the SHALs were selective for HLA-DR10 expressing malignant B-cells, showed about nM affinities, and were linearly accumulated at a fixed fractional mass/moles over the SHAL range tested. SHALs, having the Ct ligand (3-(2-([3-chloro-5-trifluoromethyl)-2-pyridinyl]oxy)-anilino)-3-oxopropanionic acid), accumulated and residualized in HLA-DR10 cells greater than accountable by cell surface HLA-DR10. Confocal microscopy confirmed intracellular residualization of these SHALs. SHALs having a Ct ligand were cytocidal at nanomolar concentrations selectively in HLA-DR10 malignant cells.

Conclusions: The results provide evidence for intracellular residualization and cytocidal effects mediated by HLA-DR10. Thus, SHALs have unique potential as novel molecules for targeting lymphoma and leukemia for molecular therapy and imaging.

Research Support: NCI PO1-CA47829 and Lawrence Livermore National Laboratory LDRD Awards 01-ERD-111, 01-ERD-046, and 01-SI-012





This Article
Services
Right arrow Email this article to a friend
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Right arrow Alert me to new issues of the journal
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Right arrow Articles by DeNardo, G.
Right arrow Articles by Balhorn, R.
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Right arrow Articles by DeNardo, G.
Right arrow Articles by Balhorn, R.