Combining therapies to combat cancer


Professor Mark Smyth

25 June 2010

In this podcast, Professor Mark Smyth of the Peter MacCallum Cancer Centre in Melbourne talks about his work researching cancer immunology.

Professor Smyth and his team are building on our understanding of how the immune system reacts to cancer, and investigating how combining conventional therapies like radiotherapy, chemotherapy with immunotherapy could have a more positive outcome for cancer patients.

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Transcript of podcast

Voice-over: Welcome to this National Health and Medical Research Council podcast. Our podcasts aim to keep you in touch with major health and medical research issues and the people who shape them.

Introduction: Hello I’m Carolyn Norrie. Today I’m speaking to Professor Mark Smyth of the Peter MacCallum Cancer Centre in Melbourne. Mark congratulations on your Australia Fellowship.

Prof Smyth: Thanks Carolyn.

Interviewer: Mark you’re working in cancer immunology, can you tell me about your work in this area.

Prof Smyth: My work is really to try and build on our understanding of how the immune system reacts to cancer, and trying to understand that in the various stages, right from the very beginning, or development of the cancer right through to the end stage when the tumour’s escaped. And the idea by learning about that process is to try and develop new therapies based on that knowledge to take to the clinic.

Interviewer: So you’re looking at taking your work into clinical practice?

Prof Smyth: Yes, our program basically spans research right from very basic fundamental tumour immunology right through to first demand clinical trials. So the Australia Fellowship is to support essentially fundamental studies in tumour immunology. Our interest there is to try and gain insight into two key mechanisms of immune control of cancer - these are new immune reactions with cancer that we first described in our group – and the questions we’re trying to answer there are really; why do only some tumours respond to immunotherapy, what makes a conventional therapy like chemotherapy or a radiotherapy capable of priming tumour immunity, and we’ve found particularly there’s an organelle in the cell, in the dendritic cell, which is the sentinel cell which detects dying cells, called the inflammasome, which appears to be important in detecting dying cells that are dying under these sorts of regimes - like chemotherapy and radiotherapy. So traditionally these therapies have been thought to act primarily by just killing cells and that was the way that they reduced tumour burden. But we’ve found now that in fact a host is involved, so the immune system gets engaged by that process and you get a priming of antigens’ specific immunity against the cancers and this is quite revolutionary. So it’s allowing us to now think about combining conventional therapies like radiotherapy, chemotherapy with immunotherapy.

Interviewer: So a somewhat different way forward in cancer treatment?

Prof Smyth: Absolutely, I mean we’ve realised that monotherapies are probably only going to be effective in a very small fraction of patients, depending on the particular pathway that they hit, whether that’s a chemotherapy or an immunotherapy for that matter. But by putting some of these pathways together we can effectively get us, you know, what we call a synergistic activity - a combined benefit greater than the added effects of either pathway, and the challenge now is to bring these combination therapies into clinical practice. So this is starting to happen already now and there are a few impediments to that process. For example that companies tend to have ownership over certain pathways and it’s a question of getting them to work together to put their particular agent of interest together with another company. But if they don’t do that, essentially the market that they have is sort of restricted to just a small group of patients that might benefit from that therapy, so we want to try and broaden the impact of certain agents by combining them with others and expanding obviously the number of patients that are going to benefit from these therapies.

Interviewer: So when you’re talking companies…is that research companies, pharmaceutical companies?

Prof Smyth: Yeah big pharmaceutical companies. They tend to have ownership over a number of the most interesting pathways. If they don’t, they’re rapidly buying those out, buying out smaller biotechs, and there’s a lot of that sort of thing going on at the moment.

Interviewer: But your work can actually help them expand the number of people they can benefit with their treatments?

Prof Smyth: Yes, absolutely, so it’s interesting that the big pharmaceuticals don’t actually have tremendous in-house capacity to do pre-clinical testing of their compounds. They tend to have certain assays that they do with their target of interest, they might be making a monoclonal antibody that they want to put into patients and they’ll test that through certain systems, but we have available in our program a large number of different mouse models of cancer which are the most clinically relevant models to use and we can set up their agents, both alone and in combination with other agents and other pathways. So very quickly we can sort of put together a picture of the potential combination therapies that might be of benefit and they can take that from there.

Interviewer: That’s great, so practical applications very early?

Prof Smyth: Yes that’s right, it’s all a matter of trying to really speed up the pipeline I guess and that’s one of the challenges. There’s a number of different immunotherapeutics and drugs in the pipeline and the challenge is trying to bring those to clinical trials as quickly as possible. There’s only obviously a limited number of patients. You always have to build on existing therapies so you know the skill is in actually trying to screen a large number of compounds quite quickly and work out which combinations are going to work in particular indications. So moving more and more towards personalised medicine really and that’s a very prudent sort of theme that we have at the Peter MacCallum (Peter MacCallum Cancer Centre in Melbourne ), it’s all about that, so there’s a number of groups here working on the genetics of cancer, trying to work out how certain tumours are made up and what the tumour microenvironment looks like in different patients and then we’re trying to obviously target the weak spots in the tumours for that particular patient with the appropriate therapy.

Interviewer: Thank you very much Professor Smyth for talking to us today. I hope your research continues to go extremely well.

Prof Smyth: Yeah thank you very much Carolyn, it’s been nice talking to you. Voice-over: This podcast was brought to you by the National Health and Medical Research Council, working to build a healthy Australia. You’ll find more information about this and other health and medical research issues on our website, at