PEPTIDE MICROARRAY FOR CANCER CELL SURFACE RECEPTORS

描述：（申请人的描述） 随着科勒和米尔斯坦（1975）发明杂交瘤技术， 许多针对细胞表面抗原的单克隆抗体（MoAb），或 受体已经被开发并在临床上用作诊断剂。在 在过去的二十年里，学术界和 制药业开发单克隆抗体来治疗人类 癌的Rituxan（抗CD 20单克隆抗体， B细胞淋巴瘤）和赫赛汀（抗乳腺癌Her 2/neu单克隆抗体）， 人类癌症的治疗已经证实了细胞表面靶向 癌症治疗的方法。评价活检标本是否存在 CD 20和Her 2/neu的检测现在是非霍奇金淋巴瘤和乳腺癌的常规检测。 癌症，分别。组合化学已经成为 近年来基础研究和药物治疗的重要技术进展 的发现可以生成数百万种化合物，并对其进行筛选。 与特定靶大分子结合或引发特异性 生物反应（Lam 1997）。在这个建议中，我们假设，通过使用 最先进“一珠一化合物”组合文库方法，我们 可以快速鉴定大量的细胞表面结合肽， 不同类型的肿瘤所特有的。我们进一步假设， 化学微阵列技术是我们实验室最近开发的， 我们可以快速表征结合特异性以及功能性 所鉴定的肽配体对大量肿瘤细胞的作用 线然后可以使用人类肿瘤特有的肽来确定 人类癌症活检标本的配体结合谱。

DESCRIPTION: (Applicant's Description) With the invention of hybridoma technology by Kohler and Milstein (1975), numerous monoclonal antibodies (MoAbs) against cell surface antigens or receptors have been developed and used clinically as diagnostic agents. In the last two decades there has been enormous effort in both academia and pharmaceutical industry to develop monoclonal antibodies to treat human cancers. The recent clinical success of Rituxan (anti-CD 20 MoAb against B-cell lymphoma) and Herceptin (anti-Her2/neu MoAb against breast cancer) in the treatment of human cancers has validated the cell-surface targeting approach for cancer therapy. Evaluation of biopsy specimens for the presence of CD20 and Her2/neu is now routinely done for non-Hodgkin lymphoma and breast cancer, respectively. Combinatorial chemistry has become one of the most important technologic advances in recent years for basic research and drug discovery. Millions of compounds can be generated and screened for their ability to bind to a specific target macromolecule or to elicit a specific biological response (Lam 1997). In this proposal, we hypothesize that by using the state-of-the-art "one-bead one-compound" combinatorial library method, we can rapidly identify a large number of cell surface binding peptides that are unique to different tumor types. We further hypothesize that with the novel chemical microarray technique that was recently developed in our laboratory, we can rapidly characterize the binding specificities as well as functional effects of the identified peptide ligands on a large number of tumor cell lines. Peptides that are unique to human tumors can then be used to determine the ligand binding profile of human cancer biopsy specimens.