Abstract
Human papillomavirus (HPV) is the primary etiologic agent of cervical cancer. Consideration of safety and non human leukocyte antigen restriction, protein vaccine has become the most likely form of HPV therapeutic vaccine, although none have so far been reported as effective. Since tumor cells consistently express the two proteins E6 and E7, most therapeutic vaccines target one or both of them. In this study, we fabricated DC vaccines by transducing replication-defective recombinant adenoviruses expressing E6/E7 fusion gene of HPV-16, to investigate the lethal effects of specific cytotoxic T lymphocytes (CTL) against CaSki cells in vitro. Mouse immature dendritic cells (DC) were generated from bone marrow, and transfected with pAd-E6/E7 to prepare a DC vaccine and to induce specific CTL. The surface expression of CD40, CD68, MHC II and CD11c was assessed by flow cytometry (FCM), and the lethal effects of CTL against CaSki cells were determined by DAPI, FCM and CCK-8 methods. Immature mouse DC was successfully transfected by pAd-E6/E7 in vitro, and the transfecting efficiency was 40%-50%. A DC vaccine was successfully prepared and was used to induce specific CTL. Experimental results showed that the percentage of apoptosis and killing rate of CaSki cells were significantly increased by coculturing with the specific CTL (p <0.05). These results illustrated that a DC vaccine modified by HPV-16 E6/E7 gene can induce apoptosis of CaSki cells by inducing CTL, which may be used as a new strategy for biological treatment of cervical cancer.
Highlights
Cervical cancer is the second most common cancer and leading cause of cancer-related death to women in worldwide (Zeng et al, 2011)
The surface expression of CD40, CD68, MHC II and CD11c was assessed by flow cytometry (FCM), and the lethal effects of cytotoxic T lymphocytes (CTL) against CaSki cells were determined by DAPI, FCM and Cell Counting Kit-8 kit (CCK-8) methods
These results illustrated that a dendritic cells (DC) vaccine modified by Human papillomavirus (HPV)-16 E6/E7 gene can induce apoptosis of CaSki cells by inducing CTL, which may be used as a new strategy for biological treatment of cervical cancer
Summary
Cervical cancer is the second most common cancer and leading cause of cancer-related death to women in worldwide (Zeng et al, 2011). Human papillomavirus (HPV) which presents in 99% of cervical cancer cases is one of the causative agents of cervical cancer (Walboomers et al, 1999). This small, non-enveloped DNA virus that infects epithelial cells of skin and mucosa, which only replicates in differentiating keratinocytes. HPV-16, is found in over 50% of squamous cell carcinomas of the uterine cervix (MildeLangosch et al, 2000; zur Hausen, 2000). Despite the recent development of various therapeutic strategies, there is no specific therapy available for invasive squamous cell carcinoma of the cervix and its precursor lesions. More efforts are needed to develop an effective therapy to achieve cure
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