Xiang J, Moyana T, Chen Z, Skinnider L, Hamilton T, Sun D
Saskatoon Cancer Center, Department of Microbiology, University of Saskatchewan, Canada.
Cancer Biother. 1993 Summer;8(2):171-80. doi: 10.1089/cbr.1993.8.171.
The genetically engineered mouse/human chimeric cB72.3m4 and cB72.3m12 antibodies all recognized the tumor-associated TAG72 antigen. The high affinity cB72.3m4 antibody had an approximately 18-fold higher affinity constant for the TAG72 antigen than the low affinity cB72.3m12 antibody. The relationship amongst antibody binding affinity, tumor binding and effector functions was studied by using these two antibodies. The data showed that the high affinity cB72.3m4 antibody was reactive with, on average, 15% more colon adenocarcinoma cells on tissue sections than the low affinity cB72.3m12 antibody, and it did not produce any cross-reactivities with various normal tissues. The high affinity cB72.3m4 antibody was able to mediate more effective ADCC and CDC to the human ovarian cancer cells in vitro than the low affinity cB72.3m12 antibody. This study provides evidence that this high affinity chimeric cB72.3m4 antibody may be useful in both immunodetection and immunotherapy of cancer.
基因工程小鼠/人嵌合cB72.3m4和cB72.3m12抗体均能识别肿瘤相关的TAG72抗原。高亲和力的cB72.3m4抗体对TAG72抗原的亲和力常数比低亲和力的cB72.3m12抗体高约18倍。利用这两种抗体研究了抗体结合亲和力、肿瘤结合与效应功能之间的关系。数据显示，高亲和力的cB72.3m4抗体在组织切片上与结肠腺癌细胞的反应性平均比低亲和力的cB72.3m12抗体高15%，且与各种正常组织无交叉反应。高亲和力的cB72.3m4抗体在体外对人卵巢癌细胞介导的ADCC和CDC比低亲和力的cB72.3m12抗体更有效。本研究提供了证据表明这种高亲和力的嵌合cB72.3m4抗体可能在癌症的免疫检测和免疫治疗中都有用。
