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| A watershed in fighting cancer – but a miracle cure is a long way off | A watershed in fighting cancer – but a miracle cure is a long way off |
| (about 1 month later) | |
| These are exciting times to be a cancer researcher. The news this week that a woman’s advanced breast cancer has apparently been eradicated by a therapy derived from her own immune system is a development many of us have waited a long time to hear. It’s personalised medicine, taken to the absolute limit, and a huge testimony to decades of hard work by a team of US researchers. And it’s the sort of advance that genuinely deserves to be called a breakthrough. | These are exciting times to be a cancer researcher. The news this week that a woman’s advanced breast cancer has apparently been eradicated by a therapy derived from her own immune system is a development many of us have waited a long time to hear. It’s personalised medicine, taken to the absolute limit, and a huge testimony to decades of hard work by a team of US researchers. And it’s the sort of advance that genuinely deserves to be called a breakthrough. |
| But those of us who treat people with advanced cancer have to balance the optimism of scientific progress with sober reality – this isn’t yet a cancer “treatment”, in the sense that is meaningful to our patients. The techniques used by Dr Steve Rosenberg’s team at the US National Cancer Institute, and which many of us in the UK (including my own team) are also working on, are fearsomely complex, and currently far outside the routine clinical reality of an NHS cancer centre. That’s not because of funding, staff levels, or any of the other criticisms often levelled at our overstretched healthcare system – it’s because of the speed with which these insights have arrived. Naturally there will be a period of catch-up while they are tested more widely, and the infrastructure to deliver them routinely is put in place. | But those of us who treat people with advanced cancer have to balance the optimism of scientific progress with sober reality – this isn’t yet a cancer “treatment”, in the sense that is meaningful to our patients. The techniques used by Dr Steve Rosenberg’s team at the US National Cancer Institute, and which many of us in the UK (including my own team) are also working on, are fearsomely complex, and currently far outside the routine clinical reality of an NHS cancer centre. That’s not because of funding, staff levels, or any of the other criticisms often levelled at our overstretched healthcare system – it’s because of the speed with which these insights have arrived. Naturally there will be a period of catch-up while they are tested more widely, and the infrastructure to deliver them routinely is put in place. |
| Doctors hail world first as woman’s advanced breast cancer is eradicated | Doctors hail world first as woman’s advanced breast cancer is eradicated |
| To understand why this genuine optimism has to be tempered with so many caveats, we need to take a look at the context surrounding the US announcement, and the recent history of cancer immunotherapy more widely. | To understand why this genuine optimism has to be tempered with so many caveats, we need to take a look at the context surrounding the US announcement, and the recent history of cancer immunotherapy more widely. |
| The idea that a patient’s own immune system has the potential to attack and control their cancer goes back decades, but treatments that could effectively kickstart this process became a reality only recently. There are now two forms of immunotherapy proven safe enough, and effective enough, for routine use. | The idea that a patient’s own immune system has the potential to attack and control their cancer goes back decades, but treatments that could effectively kickstart this process became a reality only recently. There are now two forms of immunotherapy proven safe enough, and effective enough, for routine use. |
| The first is a family of injectable antibody-based drugs that “decloak” a patient’s tumour, allowing any innate anti-cancer immune response to be unleashed. These drugs only work in a small proportion of patients with a few types of cancer – mainly, but not exclusively, those whose cancer contains extremely messy DNA. They can also cause serious side-effects. Yet when they work, the results can be dramatic – some people are still alive a decade or more later, living with forms of cancer that usually claim lives within months. | The first is a family of injectable antibody-based drugs that “decloak” a patient’s tumour, allowing any innate anti-cancer immune response to be unleashed. These drugs only work in a small proportion of patients with a few types of cancer – mainly, but not exclusively, those whose cancer contains extremely messy DNA. They can also cause serious side-effects. Yet when they work, the results can be dramatic – some people are still alive a decade or more later, living with forms of cancer that usually claim lives within months. |
| The second type of immunotherapy is known as chimeric antigen-receptor T-cell therapy, or Car-T therapy, which can treat certain patients with particular forms of blood cancer. Car-T therapy involves removing a patient’s own immune cells, genetically engineering them in the lab, and injecting them back. This is hugely expensive and technically complex, but again the outcomes can be dramatic: lethal leukaemias apparently eradicated. Unlike the aforementioned uncloaking drugs, though, Car-T cell therapy is yet to be made routinely available to cancer patients in the UK. | The second type of immunotherapy is known as chimeric antigen-receptor T-cell therapy, or Car-T therapy, which can treat certain patients with particular forms of blood cancer. Car-T therapy involves removing a patient’s own immune cells, genetically engineering them in the lab, and injecting them back. This is hugely expensive and technically complex, but again the outcomes can be dramatic: lethal leukaemias apparently eradicated. Unlike the aforementioned uncloaking drugs, though, Car-T cell therapy is yet to be made routinely available to cancer patients in the UK. |
| But many of us have suspected that there is a third avenue to immunotherapeutic success, and it’s this avenue that Rosenberg’s team have taken. Many patients have tumours that appear packed full of immune cells – soldiers present at the scene of the atrocity, so to speak, but which lack the orders to intervene. In essence, the body is acting as its own pharmaceutical company; the ability to control cancer in some patients may already be present within their tumour-immune cells which, if given a boost, are capable of controlling cancer growth. | But many of us have suspected that there is a third avenue to immunotherapeutic success, and it’s this avenue that Rosenberg’s team have taken. Many patients have tumours that appear packed full of immune cells – soldiers present at the scene of the atrocity, so to speak, but which lack the orders to intervene. In essence, the body is acting as its own pharmaceutical company; the ability to control cancer in some patients may already be present within their tumour-immune cells which, if given a boost, are capable of controlling cancer growth. |
| No chemo: the test that made me a lucky breast cancer patient | Joanna Moorhead | No chemo: the test that made me a lucky breast cancer patient | Joanna Moorhead |
| The question – seemingly answered this week – has been to find a way to isolate these rare, highly competent immune cells, then grow them in sufficient numbers to create the sort of immunological army that could tackle the billions of rogue cells that make up a tumour. | The question – seemingly answered this week – has been to find a way to isolate these rare, highly competent immune cells, then grow them in sufficient numbers to create the sort of immunological army that could tackle the billions of rogue cells that make up a tumour. |
| That’s what Rosenberg’s team have done, an extraordinary technical feat. It’s especially gratifying that their method has worked in breast cancer – a notable absentee from the list of cancer types in which current immunotherapies work, and a disease that affects tens of thousands of women each year in the UK alone. | That’s what Rosenberg’s team have done, an extraordinary technical feat. It’s especially gratifying that their method has worked in breast cancer – a notable absentee from the list of cancer types in which current immunotherapies work, and a disease that affects tens of thousands of women each year in the UK alone. |
| But as promising an avenue as this is, it’s a long and winding one – even if all subsequent technical and regulatory hurdles are cleared, it’s still only likely to be suitable for a subset of patients who, at diagnosis, have tumours already full of immune cells. We do not know how translatable these findings will be to breast cancer in general. We still don’t know why some tumours look like this, while others are immunological “deserts”. We don’t know if the latter can be converted to the former. | But as promising an avenue as this is, it’s a long and winding one – even if all subsequent technical and regulatory hurdles are cleared, it’s still only likely to be suitable for a subset of patients who, at diagnosis, have tumours already full of immune cells. We do not know how translatable these findings will be to breast cancer in general. We still don’t know why some tumours look like this, while others are immunological “deserts”. We don’t know if the latter can be converted to the former. |
| In short, there is so much we still need to learn before we can say that this brilliant success story truly heralds a new way to effectively treat our patients, who so desperately need more options than we can currently give them. | In short, there is so much we still need to learn before we can say that this brilliant success story truly heralds a new way to effectively treat our patients, who so desperately need more options than we can currently give them. |
| However, hundreds of millions of years of evolution have given us a highly competent and adaptive immune system, one that is now being used to tackle the challenge of rapidly evolving cancers – with early hints of profound benefits for patients. | However, hundreds of millions of years of evolution have given us a highly competent and adaptive immune system, one that is now being used to tackle the challenge of rapidly evolving cancers – with early hints of profound benefits for patients. |
| • Professor Charles Swanton is Cancer Research UK’s chief clinician and the founder of Achilles Therapeutics, which is developing T-cell-based cancer therapies | • Professor Charles Swanton is Cancer Research UK’s chief clinician and the founder of Achilles Therapeutics, which is developing T-cell-based cancer therapies |
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