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Understanding checkpoint blockade

An explanation of how checkpoint blockade therapies work.
SPEAKER 1: Our immune cells can mount very strong responses against abnormal cells. This is a powerful weapon against invaders, but can cause great harm if it goes out of control. To prevent this from happening, our immune cells often have checkpoint receptors on their surface, which act like little emergency stop switches. An example is a molecule called PD-1. When a target cell presses these off switches, it tells the immune cell to stop firing. One of the tricks cancer cells use to avoid immune attack is to use a molecule called PD-L1 to press PD-1 on the immune cell surface and stop it in its tracks.
A wave of new therapies are using antibody drugs to block these checkpoint receptors from being pressed and in doing so, unleash a powerful attack on the tumour by the immune cells. This new strategy is called checkpoint blockade. Checkpoint blockade has been heralded as a breakthrough in the fight against cancer. Why is that? Well, because it can produce long-lasting responses, even in patients with late stage cancer that has spread throughout the body. In contrast, responses to chemotherapy can be short-lived. Also, in principle, the strategy can be applied to a wide range of tumors.
There are many different checkpoint receptors on the immune cell surface that can dampen down their ability to kill target cells and so potentially, several different targets for checkpoint blockade therapy.
SPEAKER 2: However, checkpoint blockade is not without its problems. It depends on there being good targets on the tumour for the immune cells to recognise. So far, any subset of tumours respond to these therapies. Also, for each tumour type, only a subset of patients respond well to the therapy. Finally, the therapies are very expensive. So more research is needed to understand which patients respond to these therapies and why. If we can do this, it will help us target these expensive therapies to the right patient. And it will help us find ways to extend the success of these amazing therapies to a wider range of tumours and patients in the future.
As we’ve heard, Checkpoint Blockade therapies are beginning to have dramatic effects in some patient groups. But how do these new therapies work?
Your task: watch the video animation in which Dr Heather Long and Professor Ben Willcox explain how checkpoint blockade therapies unlock immune responses against cancer. Reflect on any new information or ideas and share your thoughts with other learners in the comments area.
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Cancer Immunotherapy: a Step Change in Cancer Treatment

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