The immunogenicity and anti-tumor effects of a lung cancer DNA vaccine harboring a MUC-1 and GM-CSF fusion gene

Yang, Zhen; Jiang, Dean; Zhu, Qiang; Xiao, Binbin; Chen, Liangan

doi:10.1590/1678-4324-2016160208

Cited by 1 publication

(2 citation statements)

References 14 publications

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“…All in all, sPD1-fusion DNA vaccine can significantly improve the anti-tumour effect, mainly because sPD1 can effectively block PD-L1 in vivo [13], which can eliminate the inhibitory effects of the PD-1/PD-L1 pathway on T cell activation. Therefore, our results support the suggestion [24] that the technique of increasing DNA vaccine immunogenicity by fusion expression of PD-1 and antigen could be considered a promising approach in anti-tumour therapy.…”

Section: Enhancement Of the Antitumour Effective In Vivosupporting

confidence: 87%

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Enhancing the antitumour-specific immunity of a lung DNA vaccine in vivo by fusion expression of MAGE-A3 and soluble PD-1

Chen

Zhang

et al. 2017

Biotechnology & Biotechnological Equipment

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Although DNA vaccines have shown a good antitumor effect in animal models, they are often not effective in clinical trials. This requires researchers to find an effective way to significantly improve the immunogenicity of vaccines. Here, we developed a new DNA vaccine based on MAGE-A3, which has been suggested as a potential target for lung cancer therapy. We enhanced the potency of this DNA vaccine by overcoming tumour-induced immunosuppressive environment through blockade of the PD-1/PD-L pathway using a soluble PD-1 (sPD1). A series of DNA plasmids encoding MAGE-A3, the extracellular domain of murine PD-1 (sPD1) and their conjugates were constructed and injected into female mice intramuscularly (i.m.) followed by an electric pulse. The humoral and cellular immune responses after immunization were evaluated by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively. To evaluate the therapeutic efficacy of the plasmids, a mouse model with a MAGE-A3-expressing tumour was designed. Mice vaccinated with the fusion expression plasmid generated the strongest MAGE-A3-specific immune responses. Furthermore, these vaccinations inhibited the growth of MAGE-A3-expressing tumours and prolonged mouse survival. These findings suggest that the combination of DNA vaccines with PD-1 pathway inhibitors may be a promising approach in clinical trials. This approach may be viable for vaccines targeting cancer, as anti-tumour vaccines have demonstrated clinical benefit but PD-1 pathway inhibitors alone have demonstrated poor efficacy so far.

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Section: Enhancement Of the Antitumour Effective In Vivosupporting

confidence: 87%

“…Therefore, the antigen targeting DC by using anti-PD-1 antibody or a soluble PD-1 can not only improve the efficiency of antigen presentation, but also block the PD-1/PD-L1 pathway. The exhaustion state of T cell function was relieved, thereby improving the immunogenicity [22][23][24].…”

Section: Enhancement Of the Antitumour Effective In Vivomentioning

confidence: 99%

Enhancing the antitumour-specific immunity of a lung DNA vaccine in vivo by fusion expression of MAGE-A3 and soluble PD-1

Chen

Zhang

et al. 2017

Biotechnology & Biotechnological Equipment

View full text Add to dashboard Cite

show abstract

The immunogenicity and anti-tumor effects of a lung cancer DNA vaccine harboring a MUC-1 and GM-CSF fusion gene

Abstract: DNA vaccines have been shown to be an effective approach to induce antigen-specific

Cited by 1 publication

References 14 publications

Enhancing the antitumour-specific immunity of a lung DNA vaccine in vivo by fusion expression of MAGE-A3 and soluble PD-1

Enhancing the antitumour-specific immunity of a lung DNA vaccine in vivo by fusion expression of MAGE-A3 and soluble PD-1

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