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AAV-sBTLA facilitates HSP70 vaccine-triggered prophylactic antitumor immunity against a murine melanoma pulmonary metastasis model in vivo
Han L.4; Wang W.2; Lu J.3; Kong F.4; Ma G.3; Zhu Y.4; Zhao D.4; Zhu J.4; Shuai W.4; Zhou Q.4; Chen P.4; Ye L.4; Tao J.4; Ahmad S.1; Li F.4; Sun J.4
2014-11-28
Source PublicationCancer Letters
ISSN18727980 03043835
Volume354Issue:2Pages:398-406
AbstractActivation of the BTLA-HVEM co-inhibitory signaling pathway impairs antitumor immunity. Our previous study demonstrated that the extracellular domain of murine BTLA (the soluble form of BTLA) can facilitate HSP70 vaccine-triggered antitumor immunity by blocking BTLA-HVEM interactions in a murine TC-1 non-metastatic tumor model. However, it is unknown whether this strategy has beneficial effects on highly malignant metastatic tumors, such as melanoma. To address this question, we expressed the soluble form of BTLA (sBTLA) in combination with HSP70 vaccine and examined the resulting antitumor activity in a melanoma pulmonary metastasis model. A recombinant adeno-associated virus (AAV) vector was used for the sBTLA gene delivery because of its high transfection efficiency and low toxicity. In vitro expression of AAV-sBTLA enhanced lymphocyte activation and induced specific cytotoxicity against B16F1 murine melanoma cells, while in vivo administration of AAV-sBTLA plus HSP70 vaccine by tail vein injection exerted a limited, late-stage antitumor effect against the existing B16F1 cells. However, the combination treatment generated a potent prophylactic antitumor response in the melanoma lung metastasis model in B6 mice. In this case, most of the metastatic foci were inhibited, and mouse survival was prolonged. Furthermore, the Th1 cytokines IL-2 and IFN-γ were up-regulated, while the negative regulatory molecules IL-10 and TGF-β were down-regulated. The number of regulatory T cells also decreased in the tumor environment. Therefore, AAV-sBTLA plus HSP70 vaccine may have therapeutic potential for the prevention of metastatic melanoma.
KeywordAAV BTLA HSP70 vaccine Immunotherapy Metastatic melanoma
DOI10.1016/j.canlet.2014.08.006
URLView the original
Language英語
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Cited Times [WOS]:7   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Florida Hospital Cancer Institute
2.Southern Medical University
3.Icahn School of Medicine at Mount Sinai
4.Tongji University
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GB/T 7714
Han L.,Wang W.,Lu J.,et al. AAV-sBTLA facilitates HSP70 vaccine-triggered prophylactic antitumor immunity against a murine melanoma pulmonary metastasis model in vivo[J]. Cancer Letters,2014,354(2):398-406.
APA Han L..,Wang W..,Lu J..,Kong F..,Ma G..,...&Sun J..(2014).AAV-sBTLA facilitates HSP70 vaccine-triggered prophylactic antitumor immunity against a murine melanoma pulmonary metastasis model in vivo.Cancer Letters,354(2),398-406.
MLA Han L.,et al."AAV-sBTLA facilitates HSP70 vaccine-triggered prophylactic antitumor immunity against a murine melanoma pulmonary metastasis model in vivo".Cancer Letters 354.2(2014):398-406.
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