Chakraborty M, Foon K A, Kohler H, Bhattacharya-Chatterjee M
Lucille Parker Markey Cancer Center, University of Kentucky Medical Center, Lexington 40536-0096, USA.
J Immunother Emphasis Tumor Immunol. 1995 Aug;18(2):95-103. doi: 10.1097/00002371-199508000-00003.
We have developed and characterized a murine monoclonal antiidiotype (Id) antibody (Ab2), designated 3H1 (IgG1-k) that mimics human carcinoembryonic antigen (CEA). 3H1 was raised against an anti-CEA monoclonal antibody (mAb) 8019 (Ab1) 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 (Ab1) 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 Ab1 (8019) for binding to CEA positive LS174-T cells, suggesting that Ab1 and Ab3 may bind to the same epitope. In addition, affinity-purified Ab3 from monkey sera immunoprecipitated the same 180,000 MW CEA as Ab1 8019 and showed an identical pattern as the Ab1 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.
我们已经开发并鉴定了一种鼠单克隆抗独特型（Id）抗体（Ab2），命名为3H1（IgG1-k），它模拟人癌胚抗原（CEA）。3H1是针对抗CEA单克隆抗体（mAb）8019（Ab1）产生的，该抗体识别180,000 MW CEA的一个独特且特异的表位。3H1在小鼠和兔子中诱导了特异性抗CEA免疫反应。在这项临床前研究中，食蟹猴（猕猴）用氢氧化铝沉淀的3H1进行免疫，并检测抗CEA抗体的诱导情况。猴子每两周皮内注射2 mg的3H1，共注射4次。所有猴子都产生了特异性抗抗独特型（Ab3）反应，该反应能够抑制免疫用的3H1（Ab2）与8019（Ab1）的结合，反之亦然。此外，猴子的免疫血清中含有Ab3（Abl'）抗体，该抗体能与CEA阳性结肠癌细胞系结合，但不与CEA阴性的MOLT-4或黑色素瘤细胞系结合。而且，Ab3与纯化的CEA反应，并与Ab1（8019）竞争结合CEA阳性的LS174-T细胞，这表明Ab1和Ab3可能结合到相同的表位。此外，从猴子血清中亲和纯化的Ab3免疫沉淀出与Ab1 8019相同的180,000 MW CEA，并且在结肠癌标本上通过免疫过氧化物酶染色显示出与Ab1相同的模式。猴子中抗肿瘤抗体的诱导未引起任何明显的副作用。这些数据表明，内影像抗独特型能够在非人灵长类动物中诱导肿瘤特异性体液免疫反应，并可作为潜在的网络抗原，在结直肠癌患者中触发活性抗CEA抗体。
