Long-term idiotype vaccination combined with interleukin-12 (IL-12), or IL-12 and granulocyte macrophage colony-stimulating factor, in early-stage multiple myeloma patients

被引:51
作者
Hansson, Lotta
Abdalla, Amir Osman
Moshfegh, Ali
Choudhury, Aniruddha
Rabbani, Hodjattallah
Nilsson, Bo
Osterborg, Anders
Mellstedt, Hakan
机构
[1] Karolinska Univ Hosp, Dept Oncol, Radiumhemmet, Stockholm, Sweden
[2] Karolinska Univ Hosp, Dept Haematol, Stockholm, Sweden
[3] Karolinska Univ Hosp, Canc Ctr Karolinska, Stockholm, Sweden
[4] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden
关键词
D O I
10.1158/1078-0432.CCR-06-1603
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose and Experimental Design: Twenty-eight patients with immunoglobulin G myeloma stages I to II were immunized i.d. over 110 weeks with autologous M protein combined with interleukin-12 (IL-12; n = 15) or with IL-12 and granulocyte macrophage colony-stimulating factor (GM-CSF; n = 13). Idiotype-specific T-cell responses were assessed by [H-3]thymidine incorporation, enzyme-linked immunospot assay, and delayed-type hypersensitivity reaction. Results: Based on these three assays, idiotype-specific immune responses were noted in 5 of 15 (33%) patients in the IL-12 group and in 11 of 13 (85%) patients in the GM-CSF/IL-12 group (P < 0.01). Immune response was seen only in patients with M-component concentration of <50 g/L. Three of 16 (19%) responders showed a gradually increasing idiotype-specific T-cell response, whereas 11 of 16 (69%) patients showed initial response, which then disappeared rapidly; the latter pattern was frequently associated with subsequent progressive disease. Immune nonresponse was associated with an increase in the numbers of CD4(+)/CD25(+) cells (regulatory T cells), which was absent in responding patients. Median time to progression for immune responders (n = 16) was 108 weeks compared with 26 weeks for nonresponders (n = 12; P = 0.03). Conclusions: These results indicate that idiotype immunization of myeloma patients with GM-CSF and IL-12 may induce specific T-cell response more frequently than with IL-12 alone and that immune response may correlate with time to progression and nonresponse with increased numbers of regulatory T cells.
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页码:1503 / 1510
页数:8
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