Rusakiewicz Sylvie, Madrigal Alejandro, Travers Paul, Dodi Anthony I
The Anthony Nolan Research Institute, The Royal Free Hospital, University College of London, Medical School, Hampstead, London NW3 2QG, UK.
Cancer Immunol Immunother. 2009 Sep;58(9):1449-57. doi: 10.1007/s00262-009-0703-x. Epub 2009 Apr 10.
The BCR/ABL p210 fusion protein has long been considered an ideal target antigen for the development of immunotherapeutic strategies in chronic myeloid leukaemia (CML) due to its central role in malignant transformation and to its unique novel amino acid sequence solely expressed in leukaemia cells. However, the feasibility to expand BCR-ABL-specific T cells remains still controversial. Using BCR/ABL peptide/MHC tetramers, significantly higher frequencies of tetramer positive cells were detected in the peripheral blood of HLA-A0301 (mean 0.38%) and HLA-B0801 (mean 0.28%) CML patients than in healthy donors (P = 0.0025 and 0.0026, respectively). However, following stimulation with autologous peptide-pulsed DCs, BCR/ABL-specific T cells were only expanded from some healthy donors, suggesting that CML patients may have a specific immune deficit with respect to the BCR/ABL antigen.
长期以来，BCR/ABL p210融合蛋白一直被认为是慢性粒细胞白血病（CML）免疫治疗策略开发的理想靶抗原，因为它在恶性转化中起核心作用，且具有仅在白血病细胞中表达的独特新氨基酸序列。然而，扩增BCR-ABL特异性T细胞的可行性仍存在争议。使用BCR/ABL肽/MHC四聚体，在HLA-A0301（平均0.38%）和HLA-B0801（平均0.28%）的CML患者外周血中检测到的四聚体阳性细胞频率显著高于健康供体（P分别为0.0025和0.0026）。然而，在用自体肽脉冲DC刺激后，仅从一些健康供体中扩增出BCR/ABL特异性T细胞，这表明CML患者可能在BCR/ABL抗原方面存在特异性免疫缺陷。
