CLONING OF IMMUNOGLOBULIN GENES TO TUMOR ANTIGENS

我们的研究工作旨在设计和建造 杂交瘤释放产生的重组免疫球蛋白基因 抗人肿瘤相关单抗 抗原。这项工作的目的是将单抗修改为：1) 降低患者的免疫原性，2)增强 单抗在患者体内的药代动力学，以及3)增加 单抗与靶抗原的结合，我们已经获得了 含重排变异体的基因组DNA重组克隆 72.3的重链和轻链基因的可能区 杂交瘤。轻链基因的核苷酸序列有 已经确定了。此外，IgKVJ序列已经被 插入含有人免疫球蛋白常量的表达载体 区域。转染该载体的细胞可表达人-鼠 嵌合体72.3免疫球蛋白类似的实验也在72.3上进行 含免疫球蛋白VDJ的重组克隆。

Our research effort is aimed at designing and constructing recombinant immunoglobulin genes derived from hybridomas releasing monoclonal antibodies (MAbs) against human tumor-associated antigens. The purpose of this effort is to modify the MAbs to: 1) reduce their immunogenicity in patients, 2) enhance the pharmacokinetics of the MAbs in patients, and 3) increase the binding of the MAb for the target antige, We have obtained recombinant clones of genomic DNA containing the rearranged vari- able regions of the heavy and light chain genes from the 72.3 hybridoma. The nucleotide sequence of the light chain gene has been determined. In addition, the IgKVJ sequences have been inserted into an expression vector containing human Ig constant region. Cells transfected with this vector express human-mouse chimeric 72.3 Ig. Similar experiments are underway with the 72.3 Ig VDJ-containing recombinant clone.