Immunotherapy in metastatic kidney cancer

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Published: 5 Dec 2013
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Dr Thomas Schwabb - Roswell Park Cancer Institute, Buffalo, USA

Dr Thomas Schwabb talks to ecancer at the 1st Indian Cancer Congress about high dose interleukin 2, a highly toxic immunotherapy treatment. At the moment there are no biomarkers to determine who will respond well to the treatment. Dr Schwabb discusses his work on researching this topic.

The challenge we have is that immunotherapy works very well for a very small number of patients with metastatic kidney cancer but the immunotherapy option we have is called high dose interleukin 2 and it is very toxic for almost all patients. One of the challenges we have is we can’t predict who will respond to high dose interleukin 2 and who won’t and so what I ultimately tried to do is give a summary of my work over the last five or six years and show how we can try to separate patients out that will respond to immunotherapy, how can we make immunotherapy better so that it’s more specific, that it works better?

Ultimately the talk was divided into two or three parts. The first part was let’s look at patients and see what the immune system looks like and how we can pull patients out that will do well with immunotherapy. So what we did is we looked at what we call lymphocytes and monocytes and we looked at their genomic profile and it turns out that patients that will respond ultimately have a completely different genomic profile in their immune cells than patients who won’t respond to immunotherapy. The second portion to the talk was that we can try to optimise the dendritic cell vaccine or the vaccine product in general and the US has a big drug on the market called Provenge or sipuleucel-T for metastatic prostate cancer and it was actually just approved in Europe as well. One of the challenges that we have with that kind of drug is patients are very heterogeneous with regards to their cell populations when they start off prior to making the drug. So can we pull out patients that have a very good pre-drug monocyte so that we can predict, hey, your vaccine is going to look really, really good? And so that was part of the talk.

Then the last part of the talk was can we improve what we call the immunogenicity, how the cancer looks to the immune system? One of the things that the immune system does is it looks for surface markers on cancer cells that we call tumour specific antigens, or target antigens, and those target antigens make the immune system realise this is a cancer cell, I need to kill it. Part of the reason why we end up with large cancers or large tumours is because the cancer is able to evade that kind of immune surveillance from the immune system. So I showed some data of how to make the cancer more attractive by giving a number of different drugs that we call hypomethylating agents or by even using radiation to change the surface structure on the cancer cells.

What about the cost of genomic testing?

The discussion I just had with that gentleman was radiation is available in almost every country so if you don’t want to do genomic testing at the very least you could try to use something as simple as radiation or a very cheap hypomethylating agent to change the immunogenicity of the cancer and put that together with immunotherapy.

Are you  looking into PD1 as well?

That came up because one of the genomic pathways that we found predicts responders versus non-responders in the immune system is related to the PD1/PDL1 pathway. As you know PD1/PDL1 right now is a very interesting pathway for what we call immune checkpoint inhibitors where we can give antibodies to that particular pathway and in some early trials those antibodies seemed to work extremely well for some cancers. In kidney cancer we’re not that sure. The other really interesting cancer for us immunotherapists is called metastatic melanoma and in that particular field those immune checkpoint inhibitors, anti-CTLA4 also called ipilimumab, or PD1/PDL1, that seems to work very well.