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Abstract:
Radioimmunolocalization of prostate cancer with radiolabeled antibodies is widely used in a clinic but radioimmunotherapy (RIT) fails to produce objective responses. Physiological barriers to the delivery of macromolecules to solid tumors are usually blamed for these failures. These studies are designed to improve the outcome of RIT in prostate adenocarcinoma by the inclusion of the antigen-independent peptides in the RIT protocol. To date two peptides able to modify vascular permeability were tested. Cytotoxicity studies indicate dose-dependent changes in cell metabolic activities after treatment with the C5aAP peptide; whereas peptide able to interact with a formyl peptide receptor-like 1 (FPRL1) does not seem to have any effect on the growth of these cells in vitro. In vivo results indicate that both peptides significantly augment RIT with 131ICC49. Three xenografts were tested to date: LNCaP, PC3 and DU145. These xenografts do not show differences in the growth pattern between the untreated tumors and peptide only-treated tumors, but there is a considerable delay in the tumor growth when peptides are combined with 131ICC49. The mechanism of this effect is more complicated than observed for LS174T tumors evaluated in the pilot studies and appears to vary depending on the tumor model and the peptide. The pattern of dependence on to key two factors emerged from these studies: (1) the improved vascular permeability and (2) the generation of reactive oxygen species.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 1 Dec 2002-30 Nov 2003 |
| Pages: |
22 |
| Report Date: |
DEC 2003 |
| Contract Number: |
DAMD17-02-1-0105 |
| Report Number: |
A672224 |
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