IMMUNOASSAYS FOR TAXOL

描述：（改编自申请人的摘要）紫杉醇是一种有前途的 一种新的抗癌药物，从西方紫杉（红豆杉）的树皮中分离出来 短叶）目前处于II期临床试验中。 进一步发展 这种药因供应不足而受阻。 新紫杉醇的鉴定 由于缺乏检测紫杉醇的合适测定法， 生物基质中的紫杉烷。 在该项目的第一阶段， 针对紫杉醇半抗原产生抗血清，并产生原型间接免疫反应。 建立了竞争抑制免疫分析法（CIEIA）。 本次CIEIA 检测树皮提取物和人体血浆中的紫杉醇，浓度低至 0.5 ng/ml。 特异性试验表明，该方法既不是紫杉醇特异性的， 也不与相关紫杉烷类化合物发生广泛交叉反应。 因此， 紫杉醇免疫测定的可行性已经被证明，现有的 基于多克隆的测定不能满足研究团体的需要。 基于单克隆抗体（MAb）的免疫测定是 问题所在 在II期研究中，紫杉醇，三尖杉宁碱， 浆果赤霉素III和10-脱乙酰基浆果赤霉素III以及对 将产生紫杉烷。 CIEIA和两种类型的现场测试， 对四种选定的紫杉烷和“通用紫杉烷”中的每一种都具有特异性， 用这些MAB开发。 目前需要分析大量的 红豆杉组织样品表明紫杉烷免疫测定法有很大的市场 可能存在。

DESCRIPTION: (Adapted from the applicant's abstract) Taxol is a promising new anti-cancer drug, isolated from the bark of the Western Yew (Taxus brevefolia) currently in Phase II clinical trials. Further development of this drug is impeded by a supply shortage. Identification of new taxol sources is hampered by the lack of suitable assays for detecting taxol and taxanes in biological matrices. In Phase I of this project, polyclonal antisera were raised against taxol haptens and a prototype indirect Competitive Inhibition Immunoassay (CIEIA) was developed. This CIEIA detects taxol in bark extracts and human plasma at concentrations down to 0.5 ng/ml. Specificity testing demonstrated that this assay was neither taxol-specific nor broadly cross-reactive with related taxanes. Thus, while the feasibility of an immunoassay for taxol has been proven, the existing polyclonal based assay does not meet the needs of the research community. Monoclonal antibody (MAb) based immunoassays are the logical solution to the problem. In Phase II study, MAbs specific for taxol, cephalomannine, baccatin III and l0-deacetylbaccatin III and MAbs with cross-reactivity for the taxanes will be produced. CIEIAs and field tests of two types, specific for each of the four selected taxanes and "generic taxane," will be developed with these MAbs. The current need to assay large numbers of Taxus tissue samples indicates a substantial market for taxane immunoassays could exist.