Accession Number:

ADA383945

Title:

Targeted Chemotherapy of Tumors and Metastases With Hyaluronic Acid-Anti-Tumor Bioconjugates

Descriptive Note:

Annual rept. 15 Jul 1999-14 Jul 2000

Corporate Author:

UTAH UNIV SALT LAKE CITY

Personal Author(s):

Report Date:

2000-08-01

Pagination or Media Count:

179.0

Abstract:

Metastatic cancer cells over-express characteristic variants of the hyaluronic acid HA receptors CD and RHAMM that mediate cell adhesion, cell motility, and cell proliferation. Rapid uptake and catabolism of HA is common in several breast cancer cell-lines. We have developed a targeted delivery system for controlled release of chemotherapeutic drugs, and we prepared HA-Taxol to test our hypothesis that HA-anti-tumor prodrugs will be more effective therapeutic agents than the unconjugated drugs. Fluorescently-labeled HA shows selective uptake, and HA-Taxol shows selective cytotoxicity to breast, colon, and ovarian cancer cells in culture it also shows release of free drug from the HA-prodrug form that is consistent with improved selectivity. Studies are in progress to i prepare an HA-brefeldin A prodrug, and ii evaluate the HA-Taxol in nude mice bearing xenografted human tumors. Chondroitin sulfate will saturate HA uptake by non-target tissues. Animal data are being obtained to support use of radiolabeled HA and HA-Taxol in Phase I clinical trials in terminal diagnosis patients. A second line of research revealed the molecular basis of the RHAMM-HA interaction, and has provided unexpected molecular leads that disrupt the oncogenic transformation of RHAMM-overexpressing cells.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE