CLONING OF ANTI-TUMOR ANTIGEN IMMUNOGLOBIN GENES AND MODIFIED CONSTRUCTS

这项研究项目的主要目标是进行基因工程 免疫球蛋白基因用于研究结构-功能关系和 产生潜在有用的免疫学试剂用于诊断和 人类肿瘤的治疗。几个杂交瘤细胞系已经被 在本实验室开发，可产生单抗(MAb) 对不同类型的肿瘤具有选择性反应。这些单抗包括 那些识别癌胚抗原的，和一种高分子的 体重，粘蛋白样癌抗原，TAG-72。单抗目前 正在接受多项诊断和治疗试验的评估 乳腺癌、结肠癌和卵巢癌。小鼠单抗B72.3及其第二代 识别TAG-72生成对应物MAB CC49已经显示 有望发展成为诊断和治疗药物。一个 阻碍鼠源性单抗临床应用的主要因素是 人抗鼠抗体(HAMA)在某些组织中的潜在免疫应答 病人。这个问题可以通过遗传方法有效地最小化。 用常量替换小鼠抗体的恒定区 人类抗体的区域以及与其他基因工程 操纵。

The main objective of this research project is to genetically engineer immunoglobulin genes to study structure-function relationships and to generate potentially useful immunological reagents for diagnosis and therapy of human tumors. Several hybridoma cell lines have been developed in this laboratory that produce monoclonal antibodies (MAbs) with selective reactivity to various tumor types. These MAbs include those that recognize carcinoembryonic antigen, and a high molecular weight, mucin-like pancarcinoma antigen, TAG-72. The MAbs are currently being evaluated in a number of diagnostic and therapeutic trials on breast, colon and ovarian cancers. The murine MAbs, B72.3 and its second generation counterpart MAb CC49, which recognize TAG-72, have shown promise for being developed into diagnostic and therapeutic agents. A major impediment to the clinical application of murine MAbs is their potential to elicit human anti-mouse antibody (HAMA) response in some patients. This problem can be effectively minimized by genetically replacing the constant region of the mouse antibody with the constant region of human antibody as well as with other genetically engineered manipulations.