Molecular Regulation of Immune Recognition Molecule Expression by Breast Cancer Cells
Abstract
Novel anti-tumor strategies are required for breast cancer. We hypothesize that immunotherapy used in a minimal residual disease setting, such as can be obtained following stem cell transplantation, may prevent relapse. Although natural killer (NK) cells are among the first immune effectors to reconstitute after transplantation, resting NK cells do not exhibit activity against breast cancer targets until activated with exogenous interleukin-2 (IL-2). To improve and develop new strategies of immunotherapy, we have investigated the mechanisms of NK cell recognition and lysis of breast cancer targets. We found that multiple mechanisms are involved, including 132 integrins CD2, and LFA-2 and Herceptin antibody dependent cytotoxicity. We have completed two clinical trials incorporating IL-2 into the autologous transplant setting. The first, exploring the combination of 1L-2 + G-CSF in stem cell mobilization, confirmed our in vitro findings that IL-2 activated NK cells are cytotoxic towards breast cancer targets, and demonstrated an enhanced anti-tumor effect of the IL-2 + G-CSF graft compared to a graft mobilized with G-CSF alone. The second clinical trial incorporated IL-2 as posttransplant immunotherapy; data is now being analyzed. We have also initiated two clinical trials, each with companion correlative studies, of other immunotherapies including Flt-3 ligand and Herceptin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA390724
Entities
People
- Linda J. Burns
Organizations
- University of Minnesota