Dabadghao S, Bergenbrant S, Anton D, He W, Holm G, Yi Q
Centre for Molecular Medicine, Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Br J Haematol. 1998 Mar;100(4):647-54. doi: 10.1046/j.1365-2141.1998.00633.x.
The monoclonal immunoglobulin (Ig) (M-component) secreted by the tumour plasma cells in multiple myeloma (MM) has specific antigenic determinants (idiotypes; id) that can serve as tumour-specific antigens. The intact Ig molecule is a weak antigen, and small fragments of id protein might be more immunogenic for the induction of id-specific immunity. Dendritic cells (DC) have attracted attention as the most efficient antigen-presenting cells and promising adjuvants for immunotherapy in tumours. In this study the in vitro T-cell response against F(ab')2 and Fab fragments, heavy and light chains of the M-component was examined in five patients with MM clinical stage I. All fragments were able to stimulate T cells but F(ab')2 or Fab fragments and heavy chains induced a stronger response than light chains. DC induced a significantly stronger id-specific immune response than monocytes. Moreover, with DC as antigen-presenting cells, a predominant interferon (IFN)-gamma (type-1 T-cell) response was seen in all patients. Both IFN-gamma and interleukin (IL)-4 (type-1 and type-2 T-cell) responses were noted when monocytes were used. Our study suggests that DC pulsed with idiotypic fragments such as F(ab')2 fragment and heavy chain can be used for the induction of type-1 anti-idiotypic T-cell response for immunotherapy in MM.
多发性骨髓瘤（MM）肿瘤浆细胞分泌的单克隆免疫球蛋白（Ig）（M成分）具有特定的抗原决定簇（独特型；id），可作为肿瘤特异性抗原。完整的Ig分子是一种弱抗原，id蛋白的小片段可能对诱导id特异性免疫更具免疫原性。树突状细胞（DC）作为最有效的抗原呈递细胞和肿瘤免疫治疗中有前景的佐剂受到关注。在本研究中，检测了5例临床I期MM患者体外针对M成分的F(ab')2和Fab片段、重链和轻链的T细胞反应。所有片段均能刺激T细胞，但F(ab')2或Fab片段以及重链诱导的反应比轻链更强。DC诱导的id特异性免疫反应明显强于单核细胞。此外，以DC作为抗原呈递细胞时，所有患者均出现主要的干扰素（IFN）-γ（1型T细胞）反应。当使用单核细胞时，观察到IFN-γ和白细胞介素（IL）-4（1型和2型T细胞）反应。我们的研究表明，用F(ab')2片段和重链等独特型片段脉冲处理的DC可用于诱导1型抗独特型T细胞反应，用于MM的免疫治疗。
