INDUCTION OF IMMUNE-RESPONSES IN PATIENTS WITH B-CELL LYMPHOMA AGAINST THE SURFACE-IMMUNOGLOBULIN IDIOTYPE EXPRESSED BY THEIR TUMORS
INDUCTION OF IMMUNE-RESPONSES IN PATIENTS WITH B-CELL LYMPHOMA AGAINST THE SURFACE-IMMUNOGLOBULIN IDIOTYPE EXPRESSED BY THEIR TUMORS
复制标题
DOI：
10.1056/nejm199210223271705
复制
发表时间：
1992-10-22
影响因子：
158.5
通讯作者：
LEVY, R
中科院分区：
文献类型：
--
作者：
KWAK, LW;CAMPBELL, MJ;LEVY, R
背景。 B细胞淋巴瘤表面免疫球蛋白的独特型决定簇可以作为克隆肿瘤特异性标记物，这可能对免疫治疗具有影响。我们试图确定是否可以在 B 细胞淋巴瘤患者中诱导针对这种自体抗原的独特型特异性免疫反应。方法。选择化疗后有微小残留病或完全缓解的九名患者。每个人都接受了一系列来自其肿瘤细胞的免疫球蛋白（免疫球蛋白独特型蛋白）的皮下注射，该免疫球蛋白已与蛋白载体缀合并与免疫佐剂混合。结果。在九名患者中的七名中，注射诱导了持续的体液型（两名患者）、细胞介导型（四名患者）或两者（一名患者）的独特型特异性免疫反应。佐剂的使用对于这些免疫反应至关重要。诱导的抗体特异性结合自体免疫球蛋白独特型，抑制鼠单克隆抗独特型抗体的结合，并结合自体肿瘤细胞。体外免疫外周血单核细胞对可溶性免疫球蛋白独特型蛋白的特异性增殖证明了细胞介导的反应。两名患有可测量疾病的患者的肿瘤均完全消退。与疫苗相关的毒性很小，仅在肌肉注射部位出现轻微反应。结论。这些结果表明，自体免疫球蛋白独特型可以在患有 B 细胞淋巴瘤的人类中配制为免疫原性、肿瘤特异性抗原，并且它们为该疾病的主动特异性免疫疗法的大规模试验提供了背景。
Background. The idiotypic determinants of the surface immunoglobulin of a B-cell lymphoma can serve as a clonal tumor-specific marker, which may have implications for immunotherapy. We sought to determine whether idiotype-specific immune responses against this autologous antigen could be induced in patients with B-cell lymphoma.Methods. Nine patients were selected who had minimal residual disease or a complete remission after chemotherapy. Each received a series of subcutaneous injections of the immunoglobulin derived from his or her tumor cells (immunoglobulin-idiotype protein), which had been conjugated to a protein carrier and mixed with an immunologic adjuvant.Results. In seven of the nine patients the injections induced sustained idiotype-specific immunologic responses of the humoral type (two patients), the cell-mediated type (four patients), or both (one patient). The use of an adjuvant was essential for these immune responses. The induced antibodies bound specifically to autologous immunoglobulin idiotype, inhibited the binding of murine monoclonal antiidiotype antibodies, and bound autologous tumor cells. Cell-mediated responses were demonstrated by the specific proliferation of immune peripheral-blood mononuclear cells to the soluble immunoglobulin-idiotype protein in vitro. The tumors of both of the patients with measurable disease regressed completely. Toxicity associated with the vaccine was minimal and consisted only of mild reactions at the site of intramuscular injection.Conclusions. These results demonstrate that autologous immunoglobulin idiotype can be formulated into an immunogenic, tumor-specific antigen in humans with B-cell lymphoma, and they provide the background for large-scale trials of active specific immunotherapy of this disease.