携带BCSG1基因的重组腺相关病毒修饰的树突状细胞制备的疫苗的免疫效果及安全性评价

Immune effect and safety evaluation of vaccine prepared by dendritic cells modified by rAAV-carrying BCSG1 gene.

作者信息

Wang W-H, Zhou C-H, Ding J, Zhang Y-X, Zheng L-L, Chen S-F, Zhang W

机构信息

Central Laboratory, Liaocheng People's Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, PRC.

Surgery of Mammary Gland and Thyroid, Liaocheng People's Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, PRC.

出版信息

Gene Ther. 2016 Dec;23(12):839-845. doi: 10.1038/gt.2016.63. Epub 2016 Aug 24.

DOI:10.1038/gt.2016.63

PMID:27556816

Abstract

The immune effect and safety evaluation of rAAV (recombinant adeno-associated virus)-containing Bcsg1 (breast cancer-specific gene 1) (rAAV/Bcsg1)-transfected DC (dendritic cell) (rAAV/Bcsg1-DC) vaccine in immunotherapy for (BCSG1) (+) BC was assessed. Immune effect of cytotoxic T lymphocytes (CTLs) on Bcsg1 (+) BC cells, and rAAV gene residuals in mature CTL cells and culture medium were determined. Nude mouse xenograft tumor model was established to assess the inhibition effects of DC-activated CTLs on tumor growth. DC cell surface markers were highly expressed in rAAV/Bcsg1 group and lysate-DC group, and rAAV/Bcsg1-DC-CTL showed stronger cytotoxic activity targeting Bcsg1 (+) BC cells. The rAAV/Bcsg1-DC vaccine-treated groups showed lower mean tumor weight, higher tumor inhibition rates and slower tumor growth. rAAV/Bcsg1-DC can induce highly efficient CTL-targeting Bcsg1 antigen without rAAV gene residuals.

摘要

评估含Bcsg1（乳腺癌特异性基因1）的重组腺相关病毒（rAAV）转染树突状细胞（DC）（rAAV/Bcsg1-DC）疫苗在（BCSG1）（+）乳腺癌免疫治疗中的免疫效果和安全性。测定细胞毒性T淋巴细胞（CTL）对Bcsg1（+）乳腺癌细胞的免疫效果，以及成熟CTL细胞和培养基中的rAAV基因残留量。建立裸鼠异种移植瘤模型，评估DC激活的CTL对肿瘤生长的抑制作用。rAAV/Bcsg1组和裂解物-DC组中DC细胞表面标志物高表达，rAAV/Bcsg1-DC-CTL对Bcsg1（+）乳腺癌细胞表现出更强的细胞毒性活性。rAAV/Bcsg1-DC疫苗治疗组的平均肿瘤重量较低，肿瘤抑制率较高，肿瘤生长较慢。rAAV/Bcsg1-DC可诱导高效靶向Bcsg1抗原的CTL，且无rAAV基因残留。