Accession Number:

ADA459211

Title:

Novel Therapeutic Approach for Breast Cancer

Descriptive Note:

Annual summary rept. 11 Jun 2003-31 May 2006

Corporate Author:

COLUMBIA UNIV NEW YORK

Personal Author(s):

Report Date:

2006-06-01

Pagination or Media Count:

62.0

Abstract:

Limitations of current viral-based cancer gene therapies include lack of cancer-specific targeting and insufficient tumor delivery. To ameliorate these problems I constructed a conditionally replication competent adenovirus CRCA manifesting the unique properties of tumor-specific virus replication and production of a cancer-selective cytotoxic cytokine, melanoma differentiation associated gene- 7interleukin-24 mda-7IL-24, which embodies potent bystander antitumor activity. Cancer cell selective tropism was ensured by engineering the expression of the adenoviral E1A protein, necessary for viral replication, under the control of the promoter of progression elevated gene-3 PEG-3 which functions selectively in diverse cancer cells with minimal activity in normal cells. In the E3 region of this CRCA we introduced the mda-7IL-24 gene, thereby mediating robust production of this cytokine as a function of adenovirus replication. Infection of this CRCA designated Ad.PEG-E1A-mda-7 in normal mammary epithelial cells and breast cancer cells confirmed cancer cell selective adenoviral replication, mda-7IL-24 expression, growth inhibition and apoptosis induction. Injecting Ad.PEG-E1A-mda-7 into human breast cancer xenografts in athymic nude mice completely eradicated not only the primary tumor but also distant tumors established on the opposite flank of the animal thereby implementing a cure. This dual cancer-specific targeting strategy provides an effective approach for treating primary and metastatic breast cancers.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE