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B7-H4 蛋白疫苗抑制小鼠 SP2/0 骨髓瘤细胞生长。

Inhibition of mouse SP2/0 myeloma cell growth by the B7-H4 protein vaccine.

机构信息

State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 17 Changle West Road, 710032 Xi'an, Shaanxi, People's Republic of China.

Experiment Teaching Center of Basic Medicine, The Fourth Military Medical University, 17 Changle West Road, 710032 Xi'an, Shaanxi, People's Republic of China.

出版信息

BMB Rep. 2014 Jul;47(7):399-404. doi: 10.5483/bmbrep.2014.47.7.168.

DOI:10.5483/bmbrep.2014.47.7.168
PMID:24314141
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4163849/
Abstract

B7-H4 is a member of B7 family of co-inhibitory molecules and B7-H4 protein is found to be overexpressed in many human cancers and which is usually associated with poor survival. In this study, we developed a therapeutic vaccine made from a fusion protein composed of a tetanus toxoid (TT) T-helper cell epitope and human B7-H4IgV domain (TT-rhB7-H4IgV). We investigated the anti-tumor effect of the TT-rhB7-H4IgV vaccine in BALB/c mice and SP2/0 myeloma growth was significantly suppressed in mice. The TT-rhB7-H4IgV vaccine induced high-titer specific antibodies in mice. Further, the antibodies induced by TT-rhB7-H4IgV vaccine were capable of depleting SP2/0 cells through complement-dependent cytotoxicity (CDC) in vitro. On the other hand, the poor cellular immune response was irrelevant to the therapeutic efficacy. These results indicate that the recombinant TT-rhB7-H4IgV vaccine might be a useful candidate of immunotherapy for the treatment of some tumors associated with abnormal expression of B7-H4.

摘要

B7-H4 是 B7 家族共抑制分子的一员，B7-H4 蛋白在许多人类癌症中过度表达，通常与不良预后相关。在这项研究中，我们开发了一种治疗性疫苗，该疫苗由破伤风类毒素 (TT) T 辅助细胞表位和人 B7-H4IgV 结构域 (TT-rhB7-H4IgV) 融合蛋白组成。我们研究了 TT-rhB7-H4IgV 疫苗在 BALB/c 小鼠中的抗肿瘤作用，发现其显著抑制了 SP2/0 骨髓瘤的生长。该 TT-rhB7-H4IgV 疫苗在小鼠中诱导了高滴度的特异性抗体。此外，TT-rhB7-H4IgV 疫苗诱导的抗体能够通过体外补体依赖性细胞毒性 (CDC) 清除 SP2/0 细胞。另一方面，细胞免疫应答不佳与治疗效果无关。这些结果表明，重组 TT-rhB7-H4IgV 疫苗可能是治疗某些与 B7-H4 异常表达相关的肿瘤的一种有前途的免疫治疗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7024/4163849/464eb9ed8445/BMB-47-399-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7024/4163849/25cbfb23da15/BMB-47-399-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7024/4163849/54236d8939f0/BMB-47-399-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7024/4163849/3451b96ef455/BMB-47-399-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7024/4163849/464eb9ed8445/BMB-47-399-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7024/4163849/25cbfb23da15/BMB-47-399-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7024/4163849/54236d8939f0/BMB-47-399-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7024/4163849/3451b96ef455/BMB-47-399-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7024/4163849/464eb9ed8445/BMB-47-399-g0004.jpg

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Oncol Rep. 2013 Nov;30(5):2442-8. doi: 10.3892/or.2013.2686. Epub 2013 Aug 22.
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Gynecol Oncol. 2012 Nov;127(2):420-5. doi: 10.1016/j.ygyno.2012.08.017. Epub 2012 Aug 19.
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Enhanced T cell immunity by B7-H4 downregulation in nonsmall-cell lung cancer cell lines.
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J Int Med Res. 2012;40(2):497-506. doi: 10.1177/147323001204000211.
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B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma.B7-H4 的表达与癌症进展相关，并可预测人食管鳞状细胞癌患者的生存情况。
Cancer Immunol Immunother. 2011 Jul;60(7):1047-55. doi: 10.1007/s00262-011-1017-3. Epub 2011 Apr 26.
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