The overall objective of this Program Project is the assessment of the role of monoclonal antibodies (MAbs) in the diagnosis, detection, and treatment of cancer. This program will focus on gastrointestinal cancers, most notably pancreatic and colorectal cancers. The Program addresses important issues in the use of antibodies on basic laboratory, preclinical, and clinical levels. Several investigators in this Program have nearly 20 years experience in the use of antibodies directed against gastrointestinal cancers. An antibody developed in this Project has a high degree of specificity for pancreatic cancer. This Project will continue its investigation of 2 antigens associated with pancreatic and colon cancers, and will refine and further test a serological immunoassay for pancreatic cancer. Preclinical studies will continue to probe for new ways to enhance the biological activity of radiolabeled antibodies. The clinical project will evaluate humanized antibodies labeled with 131I- and 90Y- as possible therapeutic agents. as well as examine several new constructs that may improve imaging. A new Project has been added to the Program. It will focus on the development of humanized antibodies, in addition to several new variants that may have diagnostic and therapeutic benefits. Humanized antibodies will reduce the immunogenicity that has been problematic for murine antibodies. In the previous year, a humanized antibody to carcinoembryonic antigen was developed and tested. A pilot clinical study determined that this agent is less immunogenic than the murine antibody. but retains excellent targeting properties. Thus, this is a highly integrated Program, supported by a number of important core laboratories. Collectively, this Program Project will help lead the way for developing new strategies for MAb-mediated detection and therapy of pancreatic and colorectal cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA054425-06
Application #
2654074
Study Section
Cancer Centers and Research Programs Review Committee (CCRP)
Program Officer
Kelsey, Morris I
Project Start
1993-02-01
Project End
2001-01-31
Budget Start
1998-03-16
Budget End
1999-01-31
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Center for Molecular Medicine/Immunology
Department
Type
DUNS #
City
Belleville
State
NJ
Country
United States
Zip Code
07950
Cardillo, Thomas M; Karacay, Habibe; Goldenberg, David M et al. (2004) Improved targeting of pancreatic cancer: experimental studies of a new bispecific antibody, pretargeting enhancement system for immunoscintigraphy. Clin Cancer Res 10:3552-61
Gold, David V; Modrak, David E; Schutsky, Keith et al. (2004) Combined 90Yttrium-DOTA-labeled PAM4 antibody radioimmunotherapy and gemcitabine radiosensitization for the treatment of a human pancreatic cancer xenograft. Int J Cancer 109:618-26
Gold, David V; Schutsky, Keith; Modrak, David et al. (2003) Low-dose radioimmunotherapy ((90)Y-PAM4) combined with gemcitabine for the treatment of experimental pancreatic cancer. Clin Cancer Res 9:3929S-37S
Reddy, P K; Gold, D V; Cardillo, T M et al. (2003) Interferon-gamma upregulates MUC1 expression in haematopoietic and epithelial cancer cell lines, an effect associated with MUC1 mRNA induction. Eur J Cancer 39:397-404
Cardillo, Thomas M; Blumenthal, Rosalyn; Ying, Zhiliang et al. (2002) Combined gemcitabine and radioimmunotherapy for the treatment of pancreatic cancer. Int J Cancer 97:386-92
Hajjar, George; Sharkey, Robert M; Burton, Jack et al. (2002) Phase I radioimmunotherapy trial with iodine-131--labeled humanized MN-14 anti-carcinoembryonic antigen monoclonal antibody in patients with metastatic gastrointestinal and colorectal cancer. Clin Colorectal Cancer 2:31-42
Modrak, David E; Rodriguez, Marisol D; Goldenberg, David M et al. (2002) Sphingomyelin enhances chemotherapy efficacy and increases apoptosis in human colonic tumor xenografts. Int J Oncol 20:379-84
O'Hara, J A; Blumenthal, R D; Grinberg, O Y et al. (2001) Response to radioimmunotherapy correlates with tumor pO2 measured by EPR oximetry in human tumor xenografts. Radiat Res 155:466-73
Gold, D V; Cardillo, T M (2001) Monoclonal antibody G47 engineered to be reactive with colorectal tumor mucin. Hybrid Hybridomics 20:343-50
Gold, D V; Cardillo, T; Goldenberg, D M et al. (2001) Localization of pancreatic cancer with radiolabeled monoclonal antibody PAM4. Crit Rev Oncol Hematol 39:147-54

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