Mannan-modified adenovirus as a vaccine to induce antitumor immunity

Abstract

Tumor vaccine is a useful strategy for cancer therapy. However, priming of the immune system requires the relevant antigen to be presented by antigen-presenting cells (APCs). Here, we employed telomerase reverse transcriptase as a model antigen to explore the feasibility of using mannan-modified adenovirus as a tumor vaccine. We found that tumor immunogene therapy with the vaccine was effective at protective antitumor immunity in mice. The antigen-specific cytotoxic T lymphocytes were found in in vitro cytotoxicity assay. The elevation of the killing activity could be abrogated by anti-CD8 or anti-major histocompatibility complex-I antibodies. Adoptive transfer of purified CD8 + cells, and CD4 + cells to a less extent, was effective at antitumor activity. In vivo antitumor activity could be abrogated by depleting CD4 + T lymphocytes. A possible explanation for the antitumor effects may be the antigen was transfered to APCs in the presence of mannan. These observations provide insights into the design of novel vaccine strategies and might be important for the future application of antigens identified in other diseases.

Mannan-modified adenovirus targeting TERT and VEGFR-2: A universal tumour vaccine

“…3). Compared with previous single antigen-encoding strategies developed in our laboratory28, the combination virus was more effective for stimulation of DCs and provided a more potent anti-tumour immune response that significantly improved survival.…”

“…Previous studies have shown that mannan modification significantly enhances antigen identification and uptake by splenic DCs28, or the lymph nodes DCs29, and leads to the activation of specific T lymphocytes. It was shown that spleen DCs could process and present antigens efficiently irrespective of the route of antigen capture30, therefore we take the convenience to manipulate and more intuitive method (spleen sections) to investigate the antigens delivering into DCs.…”

“…The conjugation of a recombinant antigen and mannan under appropriate oxidized condition can stimulate a measurable antitumor response2627. We previously constructed a mannan-modified recombinant TERT adenovirus (AdTERT-m) as a prophylactic vaccine for targeting DCs28. This virus stimulated an antigen-specific CTL response against TERT in mice that was correlated with a clear anti-tumour effect.…”

Modulation of Dendritic Cells by Nanotechnology-Based Immunotherapeutic Strategies

“…173 Mice immunized by intraperitoneal injection were apparently protected from tumor growth and the survival of the tumor-bearing mice treated with AdT-m was also longer than that of the control group. In another study, mice were immunized with DEC-205 targeted DNA vaccines and boosted with adenoviral vectors encoding OVA and HIV Gantigen-p41 as antigens.…”

“…These delivery systems are promising tools for cancer therapy, but serious concerns arise from their immunogenicity and instability in blood circulation. 165 Viruses, such as HVJ (hemagglutinating virus of Japan; Sendai virus), [166][167][168] influenza virus, 50 169 170 and adenovirus, [171][172][173] have been used in the construction of virosomes.…”