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经基因改造以表达结核分枝杆菌抗原的肿瘤细胞衍生的外泌体:一种用于癌症治疗的新型疫苗。

Exosomes derived from tumor cells genetically modified to express Mycobacterium tuberculosis antigen: a novel vaccine for cancer therapy.

作者信息

Koyama Yoshiyuki, Ito Tomoko, Hasegawa Aya, Eriguchi Masazumi, Inaba Toshio, Ushigusa Takahiro, Sugiura Kikuya

机构信息

Japan Anti-tuberculosis Association, Shin-Yamanote Hospital, 3-6-1 Suwa-cho, Higashimurayama, Tokyo, 189-0021, Japan.

Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-oraikita, Izumisano, Osaka, 598-8531, Japan.

出版信息

Biotechnol Lett. 2016 Nov;38(11):1857-1866. doi: 10.1007/s10529-016-2185-1. Epub 2016 Aug 2.

Abstract

OBJECTIVES

To examine the potential of exosomes derived from the tumor cells, which had been genetically modified to express a Mycobacterium tuberculosis antigen, as a cancer vaccine aimed at overcoming the weak immunogenicity of tumor antigens.

RESULTS

We transfected B16 melanoma cells with a plasmid encoding the M. tuberculosis antigen, early secretory antigenic target-6 (ESAT-6). The secreted exosomes bearing both tumor-associated antigens and the pathogenic antigen (or their epitopes) were collected. When the exosomes were injected into foot pads of mice, they significantly (p < 0.05) evoked cellular immunity against both ESAT-6, and B16 tumor cells. Intra-tumoral injection of the exosomes significantly suppressed (p < 0.001) tumor growth in syngeneic B16 tumor-bearing mice, while the exosomes derived from the non-transfected B16 cells showed no effect on tumor growth, although both exosomes should have similar tumor antigens.

CONCLUSIONS

Exosomes bearing both tumor antigens and the M. tuberculosis antigen (or their epitopes) have a high potential as a candidate for cancer vaccine to overcome the immune escape by tumor cells.

摘要

目的

研究经基因改造以表达结核分枝杆菌抗原的肿瘤细胞来源的外泌体作为癌症疫苗的潜力,旨在克服肿瘤抗原免疫原性较弱的问题。

结果

我们用编码结核分枝杆菌抗原早期分泌性抗原靶标6(ESAT-6)的质粒转染B16黑色素瘤细胞。收集携带肿瘤相关抗原和致病抗原(或其表位)的分泌外泌体。当将这些外泌体注射到小鼠脚垫中时,它们显著(p<0.05)激发了针对ESAT-6和B16肿瘤细胞的细胞免疫。在同基因B16荷瘤小鼠中瘤内注射外泌体显著抑制(p<0.001)肿瘤生长,而来自未转染B16细胞的外泌体对肿瘤生长无影响,尽管两种外泌体应具有相似的肿瘤抗原。

结论

携带肿瘤抗原和结核分枝杆菌抗原(或其表位)的外泌体作为癌症疫苗候选物具有很高潜力,可克服肿瘤细胞的免疫逃逸。

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