Chakraborty M, Mukerjee S, Foon K A, Köhler H, Ceriani R L, Bhattacharya-Chatterjee M
Lucille Parker Markey Cancer Center, Lexington, Kentucky.
Cancer Res. 1995 Apr 1;55(7):1525-30.
We have generated and characterized a murine monoclonal anti-idiotype (Id) antibody, designated 11D10, which biologically and antigenically mimics a distinct and specific epitope of the high molecular weight human milk fat globule primarily expressed by human breast and some other tumor cells at high density. This epitope is identified by mAb BrE1, which was used as the immunizing antibody or Ab1 to generate the anti-Id (Ab2) 11D10. 11D10 induced antitumor immune responses across species barriers, i.e., in mice and rabbits. In preclinical studies, cynomolgus monkeys were immunized with 2 mg of either 11D10 or the isotype- and allotype-matched control Ab2 3H1 after precipitation with aluminum hydroxide. All monkeys developed high titers of antibodies against the immunizing mouse immunoglobulin. Immunization with 11D10 induced anti-anti-idiotype antibodies (Ab3) which reacted with breast cancer cell lines but not with control T-cell and melanoma cell lines. The Ab3 shared idiotypes with BrE1 (Ab1), as demonstrated by their ability to inhibit 11D10 binding to BrE1. The Ab3 obtained with 11D10 bound specifically to human milk fat globule antigen and competed with BrE1 for binding to breast cancer cell lines, suggesting that Ab1 and Ab3 may bind to the same epitope. In addition, Id-specific cellular immune responses were demonstrated in monkeys immunized with 11D10 by T-cell proliferation assays. These results indicate that aluminum hydroxide-precipitated anti-Id 11D10 can induce breast cancer-specific antibodies in nonhuman primates and can serve as a potential network antigen for breast cancer patients.
我们已制备并鉴定了一种小鼠单克隆抗独特型（Id）抗体，命名为11D10，它在生物学和抗原性上模拟了高分子量人乳脂肪球的一个独特且特异的表位，该表位主要由人乳腺及其他一些肿瘤细胞高密度表达。这个表位由单克隆抗体BrE1识别，BrE1用作免疫抗体或Ab1来产生抗Id（Ab2）11D10。11D10能跨越物种屏障诱导抗肿瘤免疫反应，即在小鼠和兔子体内。在临床前研究中，食蟹猴用2毫克经氢氧化铝沉淀的11D10或同型和异型匹配的对照Ab2 3H1进行免疫。所有猴子都产生了针对免疫用小鼠免疫球蛋白的高滴度抗体。用11D10免疫诱导了抗抗独特型抗体（Ab3），其与乳腺癌细胞系反应，但不与对照T细胞和黑色素瘤细胞系反应。Ab3与BrE1（Ab1）共享独特型，这通过它们抑制11D10与BrE1结合的能力得以证明。用11D10获得的Ab3特异性结合人乳脂肪球抗原，并与BrE1竞争结合乳腺癌细胞系，表明Ab1和Ab3可能结合相同的表位。此外，通过T细胞增殖试验在接受11D10免疫的猴子中证明了Id特异性细胞免疫反应。这些结果表明，氢氧化铝沉淀的抗Id 11D10可在非人灵长类动物中诱导乳腺癌特异性抗体，并可作为乳腺癌患者潜在的网络抗原。
