期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 60, 期 2, 页码 161-171出版社
SPRINGER
DOI: 10.1007/s00262-010-0929-7
关键词
Vaccination; AML; MM; T cell; CpG; WT1
资金
- Laupitz Stiftung
- Wilhelm Sander Stiftung
- Leukemia and Lymphoma Society [LS-7008]
- NIH [CA18029, CA33084]
T cells with specificity for antigens derived from Wilms Tumor gene (WT1), Proteinase3 (Pr3), and mucin1 (MUC1) have been demonstrated to lyse acute myeloid leukemia (AML) blasts and multiple-myeloma (MM) cells, and strategies to enhance or induce such tumor-specific T cells by vaccination are currently being explored in multiple clinical trials. To test safety and immunogenicity of a vaccine composed of WT1-, Pr3-, and MUC1-derived Class I-restricted peptides and the pan HLA-DR T helper cell epitope (PADRE) or MUC1-helper epitopes in combination with CpG7909 and MontanideISA51, four patients with AML and five with MM were repetitively vaccinated. No clinical responses were observed. Neither pre-existing nor naive WT1-/Pr3-/MUC1-specific CD8(+) T cells expanded in vivo by vaccination. In contrast, a significant decline in vaccine-specific CD8(+) T cells was observed. An increase in PADRE-specific CD4(+) T helper cells was observed after vaccination but these appeared unable to produce IL2, and CD4(+) T cells with a regulatory phenotype increased. Taken into considerations that multiple clinical trials with identical antigens but different adjuvants induced vaccine-specific T cell responses, our data caution that a vaccination with leukemia-associated antigens can be detrimental when combined with MontanideISA51 and CpG7909. Reflecting the time-consuming efforts of clinical trials and the fact that 1/3 of ongoing peptide vaccination trails use CpG and/or Montanide, our data need to be taken into consideration.
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