INDUCTION OF ANTI-TUMOR IMMUNITY BY ANTI-IDIOTYPES

几个方面强调了使用抗独特型抗体的吸引力。 抗体（抗Id或Ab 2）作为癌症患者的免疫剂， 诱导癌症特异性免疫。 Ab 2疫苗是安全的，高度特异性的， 易于大量生产，并可诱导对肿瘤的免疫 通常存在耐受状态的抗原。 虽然 多克隆抗体2作为癌症免疫抑制剂的潜力 患者已被证明，在这种存在 具有未知特异性的异质性Ab 2分子群体， 不利于考虑Ab 2的临床应用 免疫接种。 因此，单克隆Ab 2将针对各种 单克隆抗人肿瘤抗体（Ab 1）， 对肿瘤细胞的优先结合反应性， 人肿瘤移植裸鼠，以及相应肿瘤的可用性 纯化形式的抗原。 在产生的各种Ab 2群体中，那些 Ab 2结合到Ab的结合位点，因此可能携带内部的 将选择相应肿瘤抗原的图像。 的潜在 以诱导跨物种的肿瘤特异性抗-抗-Id（Ab 3） 将通过用Ab 2免疫大鼠或兔来测试屏障， 与Ab 1共享独特表位并显示相同结合的Ab 3 特殊性 将测试Ab 3针对肿瘤的细胞毒性活性。 细胞培养。 由于人类肿瘤只能在免疫缺陷的 动物，将研究Ab 2免疫的肿瘤保护作用 在小鼠胸腺瘤模型系统中。 Ab 2携带胸腺瘤相关的 抗原Thy-1.2将被生产并用于肿瘤保护实验 对小鼠 此外，假设免疫疗法的有益效果 与单克隆抗肿瘤抗体在癌症患者中是通过介导的 将测试Ab 2。 我们将测试癌症中产生的Ab 2 单克隆抗体（MAb）免疫治疗过程中的患者将 诱导Ab 3和/或抗-抗-独特型T-或B-细胞的形成， 与单克隆抗体共享独特表位并显示相同的结合特异性。 这些研究将为Ab 2作为抗肿瘤药物的应用提供合理的依据。 癌症患者的免疫抑制剂。

Several aspects underscore the attraction of using anti-idiotypic antibodies (anti-Id or Ab2) as immunizing agents in cancer patients to induce cancer-specific immunity. Ab2 vaccines are safe, highly specific, easy to produce in large quantities, and may induce immunity to tumor antigens to which a state of tolerance often exists. Although the potential of polyclonal Ab2 as an immunotherapeutic agent for cancer patients has been previously demonstrated, the presence in this heterogeneous Ab2 population of molecules with unknown specificities is disadvantageous for considerations of clinical applications of Ab2 immunizations. Therefore, monoclonal Ab2 will be produced against various monoclonal anti-human tumor antibodies (Ab1) selected for their preferential binding reactivity to tumor cells, tumoricidal activity in human tumor-grafted nude mice, and availability of the corresponding tumor antigen in purified form. Of the various Ab2 populations produced, those Ab2 that bind to the combining site of Ab, and thus might bear the internal image of the corresponding tumor antigen will be selected. The potential of selected Ab2 to induce tumor-specific anti-anti-Id (Ab3) across species barriers will be tested by immunizing rats or rabbits with Ab2 to produce Ab3 sharing idiotopes with Ab1 and exhibiting identical binding specificities. The Ab3 will be tested for cytotoxic activity against tumor cells in culture. Since human tumors can only be grown in immunodeficient animals, tumor-protective effects of Ab2 immunizations will be investigated in a murine thymoma model system. Ab2 bearing the thymoma-associated antigen Thy-1.2 will be produced and used in tumor protection experiments in mice. In addition, the hypothesis that the beneficial effects of immunotherapy with monoclonal anti-tumor antibody in cancer patients are mediated through Ab2 will be tested. We will test whether the Ab2 produced in cancer patients during the course of monoclonal antibody (MAb) immunotherapy will induce the formation of Ab3 and/or anti-anti-idiotypic T- or B-cells that share idiotopes with the MAb and exhibit identical binding specificities. These studies will provide a rational basis for the use of Ab2 as immunotherapeutic agents in cancer patients.