) With the invention of hybridoma technology by Kohler and Milstein (1975), numerous monoclonal antibodies (MoAbs) against cell surface antigens or receptors have been developed and used clinically as diagnostic agents. In the last two decades there has been enormous effort in both academia and pharmaceutical industry to develop monoclonal antibodies to treat human cancers. The recent clinical success of Rituxan (anti-CD 20 MoAb against B-cell lymphoma) and Herceptin (anti-Her2/neu MoAb against breast cancer) in the treatment of human cancers has validated the cell-surface targeting approach for cancer therapy. Evaluation of biopsy specimens for the presence of CD20 and Her2/neu is now routinely done for non-Hodgkin lymphoma and breast cancer, respectively. Combinatorial chemistry has become one of the most important technologic advances in recent years for basic research and drug discovery. Millions of compounds can be generated and screened for their ability to bind to a specific target macromolecule or to elicit a specific biological response (Lam 1997). In this proposal, we hypothesize that by using the state-of-the-art """"""""one-bead one-compound"""""""" combinatorial library method, we can rapidly identify a large number of cell surface binding peptides that are unique to different tumor types. We further hypothesize that with the novel chemical microarray technique that was recently developed in our laboratory, we can rapidly characterize the binding specificities as well as functional effects of the identified peptide ligands on a large number of tumor cell lines. Peptides that are unique to human tumors can then be used to determine the ligand binding profile of human cancer biopsy specimens.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33CA089706-02
Application #
6489427
Study Section
Special Emphasis Panel (ZCA1-SRRB-C (O1))
Program Officer
Forry, Suzanne L
Project Start
2001-01-09
Project End
2003-12-31
Budget Start
2002-02-01
Budget End
2002-12-31
Support Year
2
Fiscal Year
2002
Total Cost
$316,485
Indirect Cost
Name
University of California Davis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Martin, Shiloh M; O'Donnell, Robert T; Kukis, David L et al. (2009) Imaging and pharmacokinetics of (64)Cu-DOTA-HB22.7 administered by intravenous, intraperitoneal, or subcutaneous injection to mice bearing non-Hodgkin's lymphoma xenografts. Mol Imaging Biol 11:79-87
Aina, Olulanu H; Liu, Ruiwu; Sutcliffe, Julie L et al. (2007) From combinatorial chemistry to cancer-targeting peptides. Mol Pharm 4:631-51
Marik, Jan; Lam, Kit S (2005) Peptide and small-molecule microarrays. Methods Mol Biol 310:217-26
Aina, Olulanu H; Marik, Jan; Liu, Ruiwu et al. (2005) Identification of novel targeting peptides for human ovarian cancer cells using ""one-bead one-compound"" combinatorial libraries. Mol Cancer Ther 4:806-13
Aina, Olulanu H; Marik, Jan; Gandour-Edwards, Regina et al. (2005) Near-infrared optical imaging of ovarian cancer xenografts with novel alpha3-integrin binding peptide ""OA02"". Mol Imaging 4:439-47
Xu, Qingchai; Miyamoto, Suzanne; Lam, Kit S (2004) A novel approach to chemical microarray using ketone-modified macromolecular scaffolds: application in micro cell-adhesion assay. Mol Divers 8:301-10
Liu, Ruiwu; Hsieh, Ching-Yi; Lam, Kit S (2004) New approaches in identifying drugs to inactivate oncogene products. Semin Cancer Biol 14:13-21
Liu, Ruiwu; Enstrom, Amanda M; Lam, Kit S (2003) Combinatorial peptide library methods for immunobiology research. Exp Hematol 31:11-30
DeNardo, Sally J; Yao, Zhengsheng; Lam, Kit S et al. (2003) Effect of molecular size of pegylated peptide on the pharmacokinetics and tumor targeting in lymphoma-bearing mice. Clin Cancer Res 9:3854S-64S
Lam, Kit S; Lehman, Alan L; Song, Aimin et al. (2003) Synthesis and screening of ""one-bead one-compound"" combinatorial peptide libraries. Methods Enzymol 369:298-322

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