Molecular Regulation of Immune Recognition Molecule Expression by Breast Cancer Cells
Abstract
New strategies to improve the outcome of patients with metastatic breast cancer must address the issue of residual chemotherapy-resistant cells. Immunotherapy offers the potential of manipulating effector cells to generate an enhanced anti-tumor effect. In this regard, we have demonstrated that interleukin-2 (IL-2) activated natural killer (NK) cells exhibit significant but variable cytotoxicity against five breast cancer cell lines. Little is known about receptor expression either on the breast cancer cell surface or on the NK cells which mediate NK cell killing. Our research has now demonstrated that there are independent roles of tumor cell recognition by activated NK cells through beta 2 integrins and CD2. In addition, an antibody against LFA-3, the ligand for CD2, significantly increased cytotoxicity which correlated with target cell expression of LFA-3. This effect, felt to be via ADCC, was blocked by treatment of NK with antibodies to CD2, CD18/ICAM-1, and CD16. These studies show that multiple mechanisms are involved in NK killing of breast cancer targets, and that LFA-3 mediated ADCC can target immunotherapy to breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADB244774
Entities
People
- Linda J. Burns
Organizations
- University of Minnesota