Targeting tumour vasculature by DNA vaccines

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Published: 1 Apr 2016
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Dr Andrea Facciabene - University of Pennsylvania, Philadelphia, USA

Dr Facciabene (University of Pennsylvania, Philadelphia, USA) talks to ecancertv at ITOC3 about novel TEM-1 vaccines.

The vaccine targets Tumour Endothelial Marker 1, eliminating tumour vasculature and inducing a secondary immune response.

The trials have proven effective in models of breast cancer, Lewis lung carcinoma, cervical cancer and colorectal cancer.

Host angiogenesis in wound healing and pregnancy is unaffected by the vaccine.

 

3rd Immunotherapy of Cancer Conference (ITOC3)

Targeting tumour vasculature by DNA vaccines

Dr Andrea Facciabene - University of Pennsylvania, Philadelphia, USA


The work that I talked about today, it’s targeting the vasculature but not in the classical point of view as it has been done so far but it is to instruct the immune system to recognise specifically the vasculature of the tumour and kill the already existing vasculature in the tumour. So it’s a different approach of the classical anti-angiogenetic therapy, indeed, because the anti-angiogenetic therapy blocks the formation of new vessels, vice versa this approach has the characteristic to attack the vasculature of the tumour that is already there.

What results have you seen so far?

We are demonstrating that, indeed, this vaccine is capable to induce a T-cell mediated immune response which indeed targets the vasculature of the tumour, destroying the vasculature, inducing ischaemia and inducing necrosis, apoptosis of the tumour cells. On the top of that, really interesting, is this phenomenon of cross-priming or epitope spreading that we are observing that means that killing the cell indirectly because we don’t target the cells directly with the vaccine but killing the blood vessel, blocking the of the food and the oxygen, the tumour cells die and then after that phenomena the tumour cells are also engulfed by the antigen presenting cell, by the immune system cells. Those antigen presenting cells then in return expose the tumour associated antigen so those proteins that then are capable to elicit a second immune response against the tumour itself. So it’s like we have a two pronged approach using only one vaccine.

What tumour types does this include?

At the moment we tested this with several tumours, this is also another exciting feature of this approach. Indeed, the TEM-1, it expresses the target molecule, that is tumour endothelial marker 1. We used four different models of cancer, including breast, including loose lung carcinoma, including cervical cancer and including a colorectal cancer model. In all of them we obtained the same results, we were capable to destroy the already present vasculature, block the formation of new vasculature and, on top of that, induce the secondary immune response against the tumour itself. In all of those different models we obtained similar results. This is a really nice thing because this will give us the chance to target several cancers with one single approach.

Did you see any adverse effects?

Yes, we did; we did actually. There is all of the work done because angiogenesis is a physiological process which is important for wound healing, pregnancy. And therefore of course we went to look if our therapy would have impacted pregnancy or wound healing and indeed, in animals we didn’t find any impact. There is an extra piece of information that I’m going to give to you - there is a so it doesn’t express TEM-1 and it doesn’t have an impact on wound healing or pregnancy also, confirming our data and telling us that, indeed, targeting TEM-1 seems to have no side effects on adult physiology, angiogenetic physiology.

What’s the take-home message?

The take-home message is that we are moving forward in the therapy of the cancer. There are several approaches that have been developed and the idea to target the vasculature through the immune system is also extremely exciting because it’s not like the other compounds that have been developed up to now which is specific for the vasculature but is active only in the moment you administer the drugs. This is going to be an immune response, therefore memory, therefore long-term protection. So the take-home message is that with immunotherapy we can obtain not only a reduction of the tumour, or cure in one instance, but we can get protected for the rest of our life once we use this immune response against the specific molecule that we are looking for in the cancer.