Efficient in vitro screening for drug combinations: The TEVA model

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Published: 10 Jul 2019
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Dr Angel Porgador - Ben-Gurion University of the Negev, Beersheeba, Israel

Dr Angel Porgador speaks to ecancer at the WIN 2019 Symposium in Paris about using in vitro screening to identify tailored and effective drug combinations for a patient.

Dr Porgador explains the process of using an in vitro method which uses a patient specimen to produce a patient-derived xenograft followed by an ex vivo assay.

He also discusses the issue of immunotherapy with this method in which patient T-cells can be extracted from the blood and later added to the ex vivo assay to ensure a tailored approach.

It is about the way to evaluate personalised… personalisation evaluation of the best treatment to a cancer patient. There are a lot of methods which are based on omics approaches, which is genomics, proteomics, algorithms to combine both and basically predict for a patient, based on his tumour, what would be maybe the best treatment for him. But then again in most cases these approaches can result in an unprioritised list of treatments and eventually you have to support the physician for the decision what would be the drug to give to the patient because it’s a one-time shot, not like parallel shots of five or six drugs that are recommended by the omics approach.

So we believe that the time of actually wet testing of the tumour tissue, of the patient, with the different recommendations outside of the patient is coming, is appropriate. This method maybe should be adopted at least in large medical places for better suggesting treatment options to the patients. What we devise is basically getting a specimen from the patient tumour, maybe during surgery, maybe during biopsy, implant it in mice, immune deficient mice, getting what is termed as patient-derived xenograft but then rather than expanding it and trying to test it in mice, the different drugs, suggested drugs, using just this one PDX and doing an ex vivo assay which can be done about twenty, thirty, forty singular combinations of suggested drugs and between 24 hours after possessing this PDX actually come with a more prioritised recommendation of a treatment to the physician taking care of this specific patient.

So this is what I was presenting in this meeting and I believe that eventually although the genomics, proteomics and the other omic support are developing all the time in order to analyse what would be the best, you still need some kind of wet assay to do it, to get a better evaluation of the personalised treatment.

The other thing that I was presenting is the issue of the immunotherapy in this kind of testing approach, meaning when you transfer the tumour of the patient to the mouse in order to do the ex vivo assay after, you are losing the immune system of the patient because it is not transferred to the mouse, only the tumour. So what we have done is to take in parallel from the patient blood, generate T-cells of the patient from his blood and when doing the ex vivo assay we are also adding the T-cells of the patients to the fragments. Then we actually can test combinations of immunotherapy and targeted therapy or single approaches so we can bring also the information of immunotherapy, which is a very basic pillar in the treatment of cancer today, we can add the information, the personalised tested information, also in this approach. We call this approach ITEVA – immuno-tumoural ex vivo assay – and we believe that eventually people will work with it in at least large medical centres.

What is your message for people thinking of using this method?

The message is that we are willing to teach the protocols, even for people to come to study the method in my lab. We think that this method should be adopted and should be done in different places in the world. This is not something that you can IP or something, so it’s a service that we are doing in Israel with several medical centres and we’re willing to teach others for that.