Challita-Eid P M, Penichet M L, Shin S U, Poles T, Mosammaparast N, Mahmood K, Slamon D J, Morrison S L, Rosenblatt J D
Hematology-Oncology Unit, University of Rochester Cancer Center, NY 14642, USA.
J Immunol. 1998 Apr 1;160(7):3419-26.
We describe the construction and characterization of an Ab fusion protein specific for the tumor-associated Ag HER2/neu linked to sequences encoding the extracellular domain of the B7.1 T cell costimulatory ligand. The Ab domain of the fusion molecule will specifically target HER2/neu-expressing tumor cells, while the B7.1 domain is designed to activate a specific immune response. We show that the B7.1 fusion Ab retained ability to selectively bind to the HER2/neu Ag and to the CTLA4/CD28 counter-receptors for B7.1. Specific T cell activation was observed when the B7.1 Ab fusion protein was bound to HER2/neu-expressing cells. The use of the B7.1 Ab fusion protein may overcome limitations of gene transfer and/or standard Ab therapy and represents a novel approach to the eradication of minimal residual disease.
我们描述了一种针对肿瘤相关抗原HER2/neu的抗体融合蛋白的构建和特性，该蛋白与编码B7.1 T细胞共刺激配体细胞外结构域的序列相连。融合分子的抗体结构域将特异性靶向表达HER2/neu的肿瘤细胞，而B7.1结构域旨在激活特异性免疫反应。我们表明，B7.1融合抗体保留了选择性结合HER2/neu抗原以及B7.1的CTLA4/CD28反受体的能力。当B7.1抗体融合蛋白与表达HER2/neu的细胞结合时，可观察到特异性T细胞激活。B7.1抗体融合蛋白的应用可能克服基因转移和/或标准抗体治疗的局限性，并代表了一种根除微小残留病的新方法。
