IMMUNOASSAYS FOR TAXOL

描述：(摘自申请者的摘要)紫杉醇是一种很有前途的 从红豆杉(Taxus)树皮中分离得到的抗癌新药 Brivefolia)目前处于第二阶段临床试验。进一步发展 这种药因供应短缺而受阻。新紫杉醇的鉴定 由于缺乏合适的紫杉醇和紫杉醇检测方法，来源受到阻碍 生物基质中的紫杉烷。在这个项目的第一阶段，多克隆 制备了抗紫杉醇半抗原的抗血清和间接的原型。 建立了竞争抑制免疫分析方法(CIEIA)。本CIEIA 检测树皮提取物和人血浆中紫杉醇的浓度 0.5 ng/ml。 特异性试验表明，该检测方法既不是紫杉醇专一性的 也不会与相关的紫杉烷发生广泛的交叉反应。因此，虽然 紫杉醇免疫分析的可行性已经被证明，现有的 基于多克隆的检测方法不能满足研究界的需要。 基于单抗(Mab)的免疫分析是解决 问题就在这里。在第二阶段研究中，紫杉醇、头孢甘氨酸、 巴卡菌素III和10-脱乙酰巴卡菌素III和单抗 紫杉烷将被生产出来。CIEIA和两种类型的现场试验， 对于选定的四种紫杉烷和“通用紫杉烷”中的每一种，将 是用这些单抗开发的。目前需要检测大量的 红豆杉组织样本显示紫杉烷免疫分析有相当大的市场 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.