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Targeting the ‘supply chain’ of tumour cells with DNA vaccine
A novel DNA vaccine that targets the vasculature (blood vessels) that keep tumours supplied with blood has shown promising results in mouse tumour models. The study, from researchers in the University of Pennsylvania in the USA and the University of Perugia in Italy, is published in the Journal of Clinical Investigation.

Angiogenesis is the name for the process of growth of new blood vessels from pre-existing vessels. It is an essential process in normal processes such as pregnancy, embryonic development, and wound healing. Tumour angiogenesis is a promising target for cancer therapy but previous strategies have encountered problems of specificity as processes such as wound healing were also affected. The current study identified a protein called tumour endothelial marker 1 (TEM1) as a promising target as it is overexpressed in the vasculature many tumours in both humans and mice but is expressed at low or undetectable levels in normal tissues. TEM1 is implicated in tumour vascular cell adhesion, migration and development as well as tumour progression. Its overexpression is linked to poor survival.
In the current study, the research team designed a vaccine in which Tem1 cDNA (which encodes TEM1 protein) was fused to a fragment of tetanus toxin (TT) as adjuvant in a DNA vehicle called a plasmid. This generated the Tem1-TT vaccine. The researchers tested Tem1-TT vaccine by both prophylactic and therapeutic vaccine approaches in mouse models of cancer.

In the prophylactic approach, mice were first inoculated with Tem1-TT vaccine three times at weekly intervals before being subjected to tumour challenge. The results showed that there was significant tumour protection when compared with plasmid carrying only single Tem1 or TT separately. In the therapeutic approach, the mice were first subjected to tumour challenge and then were given 3 weekly vaccinations after 3-5 days. In this case, the vascularity, or blood vessel growth, of tumours was reduced, there was increased infiltration of anti-tumour CD3+ T cells into the tumour and progression of established tumours was controlled. Importantly, the researchers established that effective Tem1-TT vaccination did not affect normal processes such as wound healing and reproduction.

In a bonus anti-tumour effect, the researchers showed that after killing the endothelial cells of the tumour vasculature, a process called epitope spreading resulted. Killing of the endothelial cells created a rich source of dead or dying tumour cells capable of inducing a cross-priming event from mouse immune cells against tumour antigens other than TEM. This process increased the therapeutic efficacy of the vaccine.

Senior author Dr Andrea Facciabene explains how this study potentially advances the field of cancer vaccines: "Until now there have been a lot of clinical trials using DNA vaccines to target tumours themselves, but unfortunately the results have been disappointing…This is a different approach which should heighten optimism for cancer vaccines in general. Moreover, based on what we’ve seen in our mouse studies, this vaccine doesn’t seem to show any significant side effects."

The authors are hopeful that targeting TEM1 will have efficacy as both a prophylactic defence against cancer and to complement therapies such as radiotherapy and chemotherapy. Dr Facciabene explains "Using this vaccine simultaneously with radiation may eventually have a double synergy…Both treatments affect the tumor endothelium, radiotherapy could help the phenomenon of epitope spreading induced by the TEM1-TT vaccine."

Future plans are to continue pre-clinical work with human TEM1 and to move on to Phase I human clinical trials.


Facciponte, J.G., Ugel, S., De Sanctis, F., Li, C., Wang, L., Nair, G., Sehgal, S., Raj, A., Matthaiou, E., Coukos, G. and Facciabene, A. Tumor endothelial marker 1–specific DNA vaccination targets tumor vasculature. J. Clin. Invest. 2014; 124(4):1497–1511 doi:10.1172/JCI67382

Press release: University of Pennsylvania School of Medicine; available at
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Targeting the ‘supply chain’ of tumour cells with DNA vaccine00