Molecular Regulation of Immune Recognition Molecule Expressionby 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 of disease. Natural killer (NK) cells reconstitute the bone marrow beginning 3-4 weeks following an autologous transplant. We determined that NK cells can be activated with exogenous interleukin-2 (IL-2) to kill breast cancer targets. In order to improve and develop new strategies of immunotherapy, we investigated the mechanisms of NK cell recognition and lysis of breast cancer targets. We found multiple mechanisms to be involved, including beta 2 integrins, CD2, and LFA-2 and Herceptin antibody dependent cytotoxicity (ADCC) . We have further investigated our ability to maximize the activation of NH cells by IL-2 in collaborative laboratory studies in the context of clinical trials. We have demonstrated IL-2 administration during stem cell mobilization enhances the immunologic potential of the graft, and that we can markedly enhance the NH lytic activity towards breast cancer targets in the post-autologous transplant period by subcutaneous IL-2 administration followed by either IL-2 activated lymphocyte infusion or bolus IL-2. A clinical trial studying our ability to translate a laboratory finding of IL-2/Herceptin ADCC into patient treatment is ongoing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA398485
Entities
People
- Linda J. Burns
Organizations
- University of Minnesota