Accession Number:

ADA439068

Title:

Breast Cancer Suppression by IDO Inhibition

Descriptive Note:

Annual rept. 1 May 2004-30 Apr 2005

Corporate Author:

LANKENAU INST OF MEDICAL RESEARCH WYNNEWOOD PA

Personal Author(s):

Report Date:

2005-05-01

Pagination or Media Count:

69.0

Abstract:

Immune escape is a crucial feature of cancer progression about which little is known. Elevation of the immunomodulatory enzyme indoleamine 2,3-dioxygenase IDO in tumor cells can facilitate immune escape. Not known is how IDO becomes elevated or whether IDO inhibitors will be useful for cancer treatment. Based on evidence that Bin1 loss elevates IDO and enhances immune evasion by tumor cells, we hypothesized that reversing IDO activity with chemical inhibitors would enhance immune recognition and rejection of tumor cells. We aimed to 1 generate an antibody to IDO to assess its expression in normal and malignant breast tissue, 2 identify pharmacologically attractive lead inhibitors of IDO, and 3 investigate the ability of new compounds with IDO inhibitory activity to block tumor growth in the MMTV-neu transgenic mouse model of breast cancer. In Year 2 of this project all Aims as proposed originally are essentially complete. This year we report new bioactive inhibitors, development of a second model for efficacy testing, and compound formulation studies. Two important outcomes this year were publication of the core findings of our study in Nature Medicine and funding of an NIH grant to drive medicinal chemistry and drug development of new lead inhibitors.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE