PEPTIDE MICROARRAY FOR CANCER CELL SURFACE RECEPTORS

描述：(申请人描述) 随着Kohler和Milstein(1975)杂交瘤技术的发明， 许多针对细胞表面抗原或 受体已被开发并用作临床诊断试剂。在 在过去的二十年里，学术界和学术界都做出了巨大的努力 制药业将开发治疗人类的单抗 癌症。抗CD20单抗Rituxan近期临床疗效观察 B细胞淋巴瘤)和赫赛汀(抗Her2/neu单抗抗乳腺癌) 人类癌症的治疗已经证实了细胞表面靶向的有效性。 癌症治疗的方法。活组织检查标本的检测 CD20和Her2/neu现在是非霍奇金淋巴瘤和乳腺的常规检查 分别是癌症。组合化学已经成为最多的 近年来基础研究和药物领域的重要技术进展 发现号。数以百万计的化合物可以产生并筛选出它们的 能够与特定的目标大分子结合或诱导特定的 生物反应(LAM 1997)。在这个提案中，我们假设通过使用 最先进的一珠一化合物组合库方法，我们 可以快速识别大量的细胞表面结合肽，这些结合肽是 是不同肿瘤类型所特有的。我们进一步假设，这部小说 我们实验室最近开发的化学微阵列技术， 我们可以快速地表征结合的特异性以及功能性 已鉴定的多肽配体对大量肿瘤细胞的作用 台词。人类肿瘤特有的多肽可以用来确定 人类癌症活检标本的配体结合图谱。

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.