Bergenbrant S, Yi Q, Osterborg A, Björkholm M, Osby E, Mellstedt H, Lefvert A K, Holm G
Immunological Research Laboratory, Karolinska Hospital, Stockholm, Sweden.
Br J Haematol. 1996 Mar;92(4):840-6. doi: 10.1046/j.1365-2141.1996.419959.x.
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 mono-clonal Ig as a 'vaccine' was shown to induce tumour-specific immunity in murine B-cell tumours and in human B-cell lymphoma. With the aim to induce or amplify an anti-idiotypic response in multiple myeloma, five stage I-III 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. In 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.
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。肿瘤B细胞表面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，因此，在肿瘤细胞克隆的免疫调节中，它是抗独特型T细胞和B细胞的潜在靶点。使用自体单克隆Ig作为“疫苗”进行主动免疫已被证明可在小鼠B细胞肿瘤和人类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增强抗独特型反应，对5例I-III期患者反复注射自体单克隆IgG。通过酶联免疫斑点试验（分泌干扰素-γ和白细胞介素-4的细胞）在体外分析独特型特异性细胞免疫。还分析了分泌抗独特型IgM抗体的B细胞。在免疫过程中，5例患者中有3例的抗独特型T细胞反应增强了1.9至5倍。这3例患者中分泌抗独特型抗体的B细胞数量也增加了。在其中2例患者中，独特型特异性免疫的诱导与血液中CD19+B细胞的逐渐减少有关。在反复免疫过程中，诱导的T细胞反应消失。有必要进一步研究以优化免疫方案，从而实现针对肿瘤克隆上独特型决定簇的持久T细胞免疫。免疫在控制肿瘤克隆中的作用仍有待确定。
