Engineering Bispecific Antibodies that Target ErbB-2 on Breast Cancer Cells.
Annual rept. 1 Sep 95-31 Aug 96,
ILLINOIS UNIV AT URBANA
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The goals of this project are to construct single-chain bispecific antibodies scFv2 that target erbB-2 on breast cancer cells, to evaluate the susceptibility of the tumor cells to lysis mediated by bispecific antibodies, and to develop an animal model that can evaluate the in vivo effectiveness of these agents. The following aims were accomplished during the past year 1 Two different scFv2 were constructed, purified, and tested in vitro. Both antibodies contained the anti-erbB-2 scFv, 800E6. One of the antibodies contained the anti-T cell receptor scFv 1B2 and the other contained the anti-V scFv KJl6. Although both scFv2 bound to the appropriate antigens, current efforts are devoted to increasing the fraction of the scFv2 that have activity. 2 Transgenic mice called TCRRAG-1- that contain a single population of cytotoxic T cells were fully characterized. The mice expressed 90 CD8 peripheral T cells, which could be activated in vitro to lyse the appropriate target cells. The TCRRAG-- mice also accepted xenografts of two erbB-2 human tumor cell lines, BT474 and SKOV3. Future work will involve strategies to activate T cells in vivo, so that the optimal conditions for tumor targeting can be explored.
- Anatomy and Physiology
- Medicine and Medical Research