Preclinical evaluation in nonhuman primates of an anti-idiotypic antibody that mimicks the carcinoembryonic antigen.
Preclinical evaluation in nonhuman primates of an anti-idiotypic antibody that mimicks the carcinoembryonic antigen.
复制标题
在非人灵长类动物中模拟癌胚抗原的抗独特型抗体的临床前评估。
DOI：
10.1097/00002371-199508000-00003
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Bhattacharya-Chatterjee,M
中科院分区：
文献类型：
--
作者：
Chakraborty,M;Foon,KA;Kohler,H;Bhattacharya-Chatterjee,M
We have developed and characterized a murine monoclonal antiidiotype (Id) antibody (Ab2), designated 3H1 (IgGl-k) that mimics human carcinoembryonic antigen (CEA). 3H1 was raised against an anti-CEA monoclonal antibody (mAb) 8019 (Abl) that recognizes a distinct and specific epitope of the 180,000 MW CEA. 3H1 induced specific anti-CEA immune responses in mice and rabbits. In this preclinical study, cynomolgus monkeys (Macaca fascicularis) were immunized with aluminum hydroxide-precipitated 3H1 and tested for the induction of anti-CEA antibodies. Monkeys were injected with 2 mg of 3H1, intracutaneously, four times biweekly. All monkeys developed specific anti-anti-Id (Ab3) responses that were capable of inhibiting binding of the immunizing 3H1 (Ab2) to 8019 (Abl) and vice versa. Furthermore, immune sera from monkeys contained Ab3 (Abl') antibody that bound to CEA-positive colon carcinoma cell lines but not to CEA-negative MOLT-4 or melanoma cell lines. Also, the Ab3 reacted with purified CEA and competed with Abl (8019) for binding to CEA positive LS174-T cells, suggesting that Abl and Ab3 may bind to the same epitope. In addition, affinity-purified Ab3 from monkey sera immunoprecipitated the same 180,000 MW CEA as Abl 8019 and showed an identical pattern as the Abl on colon carcinoma specimens by immunoperoxidase staining. The induction of anti-tumor antibodies in monkeys did not cause any apparent side effects. These data suggest that internal image anti-Id can induce tumor-specific humoral immune responses in nonhuman primates and can serve as potential network antigen for triggering active anti-CEA antibodies in colorectal cancer patients.
