Targeting of Cytolytic T-Cells for Breast Cancer Therapy Using Novel-Fusion Proteins
Annual rept. 1 Aug 96-31 Jul 99
CALIFORNIA UNIV SAN FRANCISCO
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The provision of the T cell costimulatory molecule B7 to tumor cells can be an effective means of triggering a tumor specific cytolytic T cells response. One way to provide B7 to tumor cells would be to couple an anti-tumor antibody either directly to B7 or to an antibody to the B7 counterreceptor on T cells, CD28. To this end, a fusion protein has been developed which incorporates a single chain antibody fragment scFv to erbB-2 Her2neu, an oncogene product overexpressed by 30-50 of breast carcinomas, and the extracellular domain of B7.2 CD86. This fusion protein was expressed and purified from Pichia pastoris, shown to retain binding activity to both counter receptors, erbB-2 and CD28, and shown to provide the costimulatory signal to T cells through CD28. Thus, our fusion protein was shown capable of targeting erbB-2 postive tumor cells and delivering a CD28 specific T cell costimulatory signal. Further studies should characterize the fusion protein in erbB-2 tumor bearing mice for in vivo tumor targeting, biodistribution, and efficacy.
- Medicine and Medical Research