Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients
Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients
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DOI：
10.1046/j.1365-2141.1996.419959.x
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发表时间：
1996-03-01
影响因子：
6.5
通讯作者：
Mellstedt, H
中科院分区：
文献类型：
--
作者：
Bergenbrant, S;Yi, Q;Mellstedt, H
多发性骨髓瘤的特征是克隆性B淋巴细胞和浆细胞的增殖。在肿瘤B细胞表面上表达的克隆免疫球蛋白（IG）的独特型结构可被视为肿瘤特异性抗原，并且因此，在肿瘤细胞克隆的免疫调节中，是抗独特型T和B细胞的潜在靶标。使用自体单克隆IG作为“疫苗”的主动免疫显示在小鼠B细胞瘤和人B细胞淋巴瘤中诱导肿瘤特异性免疫。为了在多发性骨髓瘤中诱导或扩增抗独特型应答，用自体单克隆IgG重复免疫Eve I-VI期患者。通过酶联免疫斑点试验（干扰素-γ和白细胞介素-4分泌细胞）在体外分析独特型特异性细胞免疫的诱导。还分析了分泌抗独特型IgM抗体的B细胞。在免疫过程中，5名患者中有3名的抗独特型T细胞反应扩增了1.9-5倍。这三名患者分泌抗独特型抗体的B细胞数量也增加。其中2例患者的独特型特异性免疫诱导与血液CD 19（+）B细胞的逐渐减少有关。诱导的T细胞应答在重复免疫期间被消除。进一步的研究是必要的，以优化免疫接种计划，以实现持久的T细胞免疫对肿瘤克隆的独特型决定因素。免疫在控制肿瘤克隆中的作用仍有待确定。
Multiple myeloma is characterized by a proliferation of clonal B lymphocytes and plasma cells. The idiotypic structure of clonal immunoglobulin (Ig) expressed on the tumour B-cell surface can be regarded as a tumour-specific antigen and, as such, a potential target for anti-idiotypic T and B cells in an immune regulation of the tumour-cell clone. Active immunization using the autologous monoclonal Ig as a 'vaccine' was shown to induce tumour-specific immunity in murine B-cell rumours and in human B-cell lymphoma. With the aim to induce or amplify an antiidiotypic response in multiple myeloma, Eve stage I-VI patients were repeatedly immunized with the autologous monoclonal IgG. induction of idiotype-specific cellular immunity was analysed in vitro by an enzyme-linked immunospot assay (interferon-gamma and interleukin-4 secreting cells). B cells secreting anti-idiotypic IgM antibodies were also analysed. An anti-idiotypic T-cell response was amplified 1.9-5-fold in three of the five patients during immunization. The number of B cells secreting anti-idiotypic antibodies also increased in these three patients. Ln two of the patients induction of idiotype-specific immunity was associated with a gradual decrease of blood CD19(+) B cells. The induced T-cell response was eliminated during repeated immunization. Further studies are warranted to optimize the immunization schedule in order to achieve a long-lasting T-cell immunity against idiotypic determinants on the tumour clone. A role for immunity in controlling the tumour clone remains to be established.