BIFUNCTIONAL ANTIBODY MEDIATED NEUTRON CAPTURE THERAPY

描述（改编自申请人的摘要）： 该项目的目标是开发利用双特异性 用于肿瘤中硼-10原子选择性浓缩的免疫蛋白 硼中子俘获疗法（BNCT）。 双特异性 本项目研究的免疫蛋白将对以下方面具有特异性： 肿瘤相关抗原（CEA）和巢状碳硼烷半抗原。 该项目的重点是发展表达方法， 双特异性免疫蛋白的基因工程方法。 的基因 编码抗巢抗体和抗CEA抗体的抗体现在可用于 操纵 在进行旨在开发最佳 双特异性免疫蛋白递送系统，申请人还打算 开展旨在开发最佳相应富硼 含有半抗原的大分子。 富含硼的大分子 研究将基于磷酸二酯或多肽 骨干 申请人开发了灵活有效的方法， 这两种类型的化合物的合成，其可以包含 许多半抗原样巢状碳硼烷基残基。 申请人会 研究这些化合物是否可以通过预靶向定位在肿瘤中 体内针对肿瘤细胞的双特异性免疫蛋白， 富含硼的大分子 这种方法将根据 其中大分子将预结合到双特异性抗体上， 然后随后在体内给药。 的抗肿瘤功效 BNCT中的双特异性抗体将在携带CEA+的小鼠中进行评价， CEA-肿瘤。

DESCRIPTION (Adapted from the Applicant's Abstract): The long-term objective of this project is to develop the means to utilize bi-specific immunoproteins for the selective concentration of boron-10 atoms in tumors for the boron neutron capture therapy (BNCT) of cancer. The bi-specific immunoproteins to be investigated in this project will have specificity for both a tumor-associated antigen (CEA) and a nido-carboranyl hapten. The project is focused on the development of methods for the expression of bi-specific immunoproteins using a genetic engineering approach. The genes encoding the anti-nido antibody and anti-CEA antibody are now available for manipulation. While performing research aimed at the development of optimal bi-specific immunoprotein delivery systems, the applicants intend to also conduct research aimed at developing optimal corresponding boron-rich hapten-containing macro molecules. The boron-rich macro molecules to be investigated will be based upon either a phosphate diester or polypeptide backbone. The applicants have developed flexible and efficient methods for the syntheses of both of these types of compounds, which can contain numerous hapten-like nido-carboranyl residues. The applicants will investigate whether these compounds can localize in tumor by pre-targeting bi-specific immunoprotein to tumor cells in vivo and then administering boron-rich macro molecules. This approach will be evaluated against one in which the macro molecules will be pre-bound to the bi-specific antibody and then subsequently administered in vivo. The anti-tumor efficacy of bi-specific antibodies in BNCT will be evaluated in mice bearing CEA+ and CEA- tumors.