Abstract

The scientific community has been excited for the past decade by the potential of cancer therapy with Monoclonal Antibodies, either alone or as immunoconjugates with drugs, toxins, or radionuclides. In spite of the specific cancer cell targeting and in vitro antibody cytotoxicity for cancer cells, results of clinical trials in cancer patients have been generally disappointing. The goal of this project is to develop a therapeutic approach to metastatic breast carcinoma with combined radioimmunoconjugates and other BRM's, to be studied by quantitative methods and combined in dose levels and sequences that are based on the pharmacokinectic data ad optimal tumor uptake, therapeutic ratio, and tumor response. Using tumor uptake (delivery) of pharmaceutical as the 'gold standard' we will determine the optimal biological dose (OBD) as well as optimal timing of the sequential doses to maximize the tumor dose. The tumor uptake and the effects of radioimmunoconjugate therapy delivered in this manner will be then compared to the tumor uptake and response when further BRM's are added in sequence under the same quantitative scrutiny.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA047829-03
Application #
3813034
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
University of California Davis
Department
Type
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618

  Publications

Schellinger, Joan G; Kudupudi, Avinash; Natarajan, Arutselvan et al. (2012) A general chemical synthesis platform for crosslinking multivalent single chain variable fragments. Org Biomol Chem 10:1521-6
Saludes, Jonel P; Natarajan, Arutselvan; DeNardo, Sally J et al. (2010) The remarkable stability of chimeric, sialic acid-derived alpha/delta-peptides in human blood plasma. Chem Biol Drug Des 75:455-60
Kumaresan, Pappanaicken R; Luo, Juntao; Lam, Kit S (2009) On-demand cleavable linkers for radioimmunotherapy. Methods Mol Biol 539:191-211
DeNardo, G L; Mirick, G R; Hok, S et al. (2009) Molecular specific and cell selective cytotoxicity induced by a novel synthetic HLA-DR antibody mimic for lymphoma and leukemia. Int J Oncol 34:511-6
Balhorn, Rod; Hok, Saphon; DeNardo, Sally et al. (2009) Hexa-arginine enhanced uptake and residualization of selective high affinity ligands by Raji lymphoma cells. Mol Cancer 8:25
Sulchek, Todd; Friddle, Raymond; Ratto, Timothy et al. (2009) Single-molecule approach to understanding multivalent binding kinetics. Ann N Y Acad Sci 1161:74-82
DeNardo, Gerald L; Natarajan, Arutselvan; Hok, Saphon et al. (2008) Nanomolecular HLA-DR10 antibody mimics: A potent system for molecular targeted therapy and imaging. Cancer Biother Radiopharm 23:783-96
Natarajan, Arutselvan; Xiong, Cheng-Yi; Gruettner, Cordula et al. (2008) Development of multivalent radioimmunonanoparticles for cancer imaging and therapy. Cancer Biother Radiopharm 23:82-91
Lehmann, Joerg; Natarajan, Arutselvan; Denardo, Gerald L et al. (2008) Short communication: nanoparticle thermotherapy and external beam radiation therapy for human prostate cancer cells. Cancer Biother Radiopharm 23:265-71
Kumaresan, Pappanaicken R; Luo, Juntao; Song, Aimin et al. (2008) Evaluation of ketone-oxime method for developing therapeutic on-demand cleavable immunoconjugates. Bioconjug Chem 19:1313-8

Showing the most recent 10 out of 187 publications