Chaux P, Vantomme V, Coulie P, Boon T, van der Bruggen P
Ludwig Institute for Cancer Research, and Cellular Genetics Unit, Catholic University of Louvain, Brussels, Belgium.
Int J Cancer. 1998 Aug 12;77(4):538-42. doi: 10.1002/(sici)1097-0215(19980812)77:4<538::aid-ijc11>3.0.co;2-2.
Attempts to detect a cytolytic T-lymphocyte (CTL) response in melanoma patients vaccinated with MAGE-3 peptides have been negative so far, even though some tumor regressions have been observed. The detection of such responses may require very sensitive detection assays for CTL precursors. To this end, we set up a method whereby a large number of CD8+ T-cell microcultures are stimulated with autologous antigen-presenting cells incubated with a peptide, in the presence of interleukin (IL)-6 and IL-12 during the first week, and IL-2 and IL-7 from the second week. We report here that not only monocyte-derived dendritic cells but also activated T cells incubated with the MAGE-3 antigenic peptide presented by HLA-A2 were effective in activating specific CTL precursors present in the blood of individuals without cancer. These precursors were detected in the CD8+ CD45RA+ subpopulation of T cells. Among the CD8+ T-lymphocyte population of blood donors, the frequency of CTL precursors specific for the MAGE-3.A2 antigen ranged from 4 to 17 x 10(-7). For the MAGE-3 antigenic peptide presented by HLA-A1, this frequency ranged from 0.4 to 3 x 10(-7). Knowing that several parameters of this procedure still have to be optimized, we will begin to use it to evaluate the CTL precursor frequencies of cancer patients before and after injection of MAGE peptides.
尽管观察到一些肿瘤消退现象，但迄今为止，在用MAGE-3肽进行疫苗接种的黑色素瘤患者中检测细胞溶解性T淋巴细胞（CTL）反应的尝试均为阴性。检测此类反应可能需要非常灵敏的CTL前体细胞检测方法。为此，我们建立了一种方法，即大量CD8+ T细胞微培养物用与肽一起孵育的自体抗原呈递细胞刺激，第一周存在白细胞介素（IL）-6和IL-12，第二周起存在IL-2和IL-7。我们在此报告，不仅单核细胞衍生的树突状细胞，而且与由HLA-A2呈递的MAGE-3抗原肽一起孵育的活化T细胞，在激活无癌症个体血液中存在的特异性CTL前体细胞方面均有效。这些前体细胞在T细胞的CD8+ CD45RA+亚群中被检测到。在献血者的CD8+ T淋巴细胞群体中，对MAGE-3.A2抗原特异的CTL前体细胞频率范围为4至17×10⁻⁷。对于由HLA-A1呈递的MAGE-3抗原肽，该频率范围为0.4至3×10⁻⁷。鉴于此程序的几个参数仍需优化，我们将开始用它来评估癌症患者在注射MAGE肽前后的CTL前体细胞频率。
