del Campo A B, Aptsiauri N, Méndez R, Zinchenko S, Vales A, Paschen A, Ward S, Ruiz-Cabello F, González-Aseguinolaza G, Garrido F
Departamento de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Granada.
Scand J Immunol. 2009 Aug;70(2):125-35. doi: 10.1111/j.1365-3083.2009.02276.x.
Here we report a successful use of a non-replicating adenovirus expressing the wild-type human beta2m gene in recovery of normal human leucocyte antigen (HLA) class I expression in beta2m-null cancer cells. Total loss of HLA class I expression in these cell lines is caused by a mutation in beta2m gene and a loss of heterozygosity in chromosome 15 carrying another copy of that gene. Normal HLA class I expression on the tumour cell surface is critical for the successful outcome of cancer immunotherapy as T cells can only recognize tumour-derived peptides in a complex with self-HLA class I molecules. In this report we characterize the newly generated adenoviral vector AdCMVbeta2m and demonstrate an efficient beta2m gene transfer in tumour cell lines of different histological origin, including melanoma, prostate and colorectal carcinoma. The beta2m re-expression lasted for an extended period of time both in vitro and in vivo in human tumour xenograft transplants. We propose that in a subset of cancer patients with structural defect in beta2m gene or chromosome 15, the adenoviral-mediated recovery (or even increase) of HLA class I expression on tumour cells in combination with vaccination or adoptive T-cell therapy can provide a complementary approach to improve the clinical efficacy of cancer immunotherapy.
在此，我们报告了一种非复制型腺病毒的成功应用，该腺病毒表达野生型人β2微球蛋白（β2m）基因，可使β2m基因缺失的癌细胞恢复正常的人类白细胞抗原（HLA）I类表达。这些细胞系中HLA I类表达的完全丧失是由β2m基因突变以及携带该基因另一个拷贝的15号染色体杂合性缺失所致。肿瘤细胞表面正常的HLA I类表达对于癌症免疫治疗的成功结果至关重要，因为T细胞只能识别与自身HLA I类分子结合的肿瘤衍生肽。在本报告中，我们对新构建的腺病毒载体AdCMVβ2m进行了表征，并证明其能在不同组织学来源的肿瘤细胞系（包括黑色素瘤、前列腺癌和结直肠癌）中高效转移β2m基因。β2m的重新表达在体外和体内的人肿瘤异种移植中都持续了较长时间。我们提出，在一部分β2m基因或15号染色体存在结构缺陷的癌症患者中，腺病毒介导的肿瘤细胞HLA I类表达的恢复（甚至增加），与疫苗接种或过继性T细胞疗法相结合，可为提高癌症免疫治疗的临床疗效提供一种补充方法。
