The overall goals of this proposal are to create more effective antibody like forms for human tumor therapy and to determine why p185her2/neu caused tumors become more genetically abnormal over time.
The aims are (1) To create small antibody-like molecules that will have an extended therapeutic half-life and can penetrate tumor mass and promote ADCC by preferential interactions with stimulatory Fc Receptors and (2) To characterize the erbB and Survivin pathways leading to tumor aneuploidy. The hypothesis that small, tumor mass permeating antibody forms with intermediate levels of affinities (e.g.10-7 M) will be more efficacious in eradicating erbB transformed cells will be evaluated. Moreover, the hypothesis that Survivin and erbB expression patterns leads to progressive aneuploidy and its reversal by intact antibody smaller dimer-inhibiting antibody forms will be tested. The intention is to focus on progress made in the current proposal that defines the minimal antibody forms that can reverse the malignant phenotype of erbB transformed cells.

Public Health Relevance

A change in our understanding of how to create optimal targeted therapeutics has evolved. The goal of this grant is to improve the targeted therapeutics of erbB caused tumors that have led to already approved, but not optimally effective, therapies. Application of these newer therapies to prevent tumor progression will be analyzed.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA055306-17
Application #
8138644
Study Section
Cancer Immunopathology and Immunotherapy Study Section (CII)
Program Officer
Howcroft, Thomas K
Project Start
1992-05-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2013-07-31
Support Year
17
Fiscal Year
2011
Total Cost
$261,108
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Fu, Weihua; Madan, Elena; Yee, Marla et al. (2012) Progress of molecular targeted therapies for prostate cancers. Biochim Biophys Acta 1825:140-52
Ponde, Datta E; Su, ZiFen; Berezov, Alan et al. (2011) Development of anti-EGF receptor peptidomimetics (AERP) as tumor imaging agent. Bioorg Med Chem Lett 21:2550-3
Liu, Qingdu; Hirohashi, Yoshihiko; Du, Xiulian et al. (2010) Nek2 targets the mitotic checkpoint proteins Mad2 and Cdc20: a mechanism for aneuploidy in cancer. Exp Mol Pathol 88:225-33

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