INDUCTION OF ANTI-TUMOR IMMUNITY BY ANTI-IDIOTYPES

有几个方面强调了使用抗独特型药物的吸引力 抗体(抗ID或AB2)在癌症患者中的免疫作用 诱导癌症特异性免疫。AB2疫苗是安全、高度特异的， 容易大量生产，并可能诱导对肿瘤的免疫 通常存在耐受状态的抗原。尽管 多克隆抗体Ab2作为肿瘤免疫治疗剂的潜力 患者之前已经被证明，这一点的存在 未知特性的非均相AB2分子群体是 不利于考虑AB2的临床应用 免疫接种。因此，将产生针对各种不同病毒的单克隆ab2。 抗人肿瘤单抗(AB1)被选作 对肿瘤细胞的优先结合反应，杀瘤活性 人肿瘤裸鼠移植瘤及相应肿瘤的可获得性 纯化形式的抗原。在生产的各种AB2种群中，那些 结合到抗体的结合部位的AB2，因此可能带有内部 将选择相应肿瘤抗原的图像。潜力 以诱导跨物种的肿瘤特异性抗-抗ID(Ab3) 屏障将通过用AB2免疫老鼠或兔子来测试，以产生 Ab3与ab1共享独特位并表现出相同的结合 具体细节。将对ab3进行抗肿瘤细胞毒活性测试。 培养中的细胞。由于人类肿瘤只能在免疫缺陷的环境中生长 动物，AB2免疫的肿瘤保护作用将被调查 在小鼠胸腺瘤模型系统中。携带胸腺瘤相关基因的AB2 将生产Thy-1.2抗原并用于肿瘤保护实验 在老鼠身上。 此外，关于免疫疗法的有益效果的假说 肿瘤患者体内的抗肿瘤单抗是通过 AB2将接受测试。我们将测试AB2是否在癌症中产生 患者在单抗(Mab)免疫治疗过程中 诱导ab3和/或抗独特型T或B细胞的形成 与单抗共享独特位，并表现出相同的结合特异性。 这些研究将为AB2作为 癌症患者的免疫治疗药物。

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.