Breast Cancer Suppression by IDO Inhibitors
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 IDO antibody to assess its expression in normal and malignant breast tissue, (2) identify pharmacologically attractive 'lead' inhibitors of IDO, and (3) evaluate the ability of compounds with IDO inhibitory activity to block tumor growth in the MMTV-neu mouse model of breast cancer. In Year 3 of this project we report progress beyond the Aims as originally proposed, which were completed last year. Briefly, we report progress on new inhibitors and findings related to compound formulation, mechanism, and efficacy. This highly successful project has helped drive the efforts of a multidisplinary team of government, biotech, and academic groups who are collaborating to move a lead IDO inhibitor into Phase I clinical trials later this year.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2006
- Accession Number
- ADA457476
Entities
People
- George C. Prendergast