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Skip to 0 minutes and 14 seconds STEVE LEE: Hello. My name is Steve Lee, and I’m a senior research fellow here at the University of Birmingham. As you’ve heard previously, T cells carry a T cell receptor that enables them to recognise fragments of proteins. And some of these can recognise proteins expressed on cancer. However, sadly, in many cancer patients, such T cells a too few in number, and can’t function very well, so they’re unable to control the tumour. Therefore, one approach to treat these patients is to use genetic engineering to reprogram large numbers of their T cells, so that many more of them can now recognise and destroy the cancer. We can do this reprogramming of T cells in two different ways.

Skip to 1 minute and 2 seconds One approach is to introduce a gene that encodes a new T cell receptor, one that can recognise a protein on the cancer cell. The other approach is to introduce a gene that encodes what we call a chimeric antigen receptor, or CAR. A CAR is a fusion between an antibody that recognises cancer cells, and the signalling component of the T cell receptor. So when a T cell engineered to express such a CAR encounters a cancer cell, the antibody component binds to the cancer, and this will then deliver a signal to the T cell, causing it to kill that cancer cell. Key to the success of using these engineered T cells is the selection of an appropriate target protein.

Skip to 1 minute and 51 seconds Ideally, this protein must be expressed on all cancer cells, in lots of cancer patients, but not expressed on healthy, normal tissue. Otherwise, targeting this protein may lead to toxicity. Furthermore, the protein needs to be important for the growth and/or survival of the cancer, or you may only kill off some of the tumour cells, and others– that don’t express the protein– will grow and take their place. In the last few years, several clinical trials have explored the use of genetically reprogrammed T cells to treat cancer patients. The results have been remarkable, particularly when using CAR-expressing T cells to treat blood cancers.

Skip to 2 minutes and 35 seconds What these trials have shown is that the engineered T cells are very potent, and in several trials, the tumours have disappeared in 80% to 90% of terminally ill cancer patients. But there are some key challenges that remain. In particular, we still need to find better targets to avoid damaging normal tissues, and we need to find ways of extending the success seen with blood cancers to the so-called solid tumours, like liver, lung, breast, and pancreatic cancer. In my lab, we’re exploring the use of CAR-expressing T cells. But rather than targeting the cancer cells directly, we’re trying to attack the blood vessels that support them.

Skip to 3 minutes and 20 seconds Working with another research group, based here at the University of Birmingham, and led by Professor Roy Bicknell, we’re identifying markers, selectively expressed on the blood vessels within tumours, and then designing CARs to attack these vessels. In this way, we hope to destroy the cancer’s support structure, effectively depriving the cancer of the oxygen and nutrients that it needs to grow. Encouragingly, some of these markers are expressed on the blood vessels of many different solid tumours, so potentially, this approach could be used to treat many cancer patients. And we’ve recently received significant funding from the Cell and Gene Therapy Catapult to develop this strategy, and then test it in clinical trials.

Skip to 4 minutes and 6 seconds This highlights the potential for so-called bench to bedside research here at the University of Birmingham, and through the [? CIC, ?] where we can take new ideas to treat cancer and develop them through laboratory studies from fundamental science, to target discovery, therapeutic development, and ultimately through to clinical trials. So these are very exciting times for using genetically engineered T cells to treat cancer, and in the near future, I’m sure we will see many more trials exploring this approach. But hopefully we will also see the development of more refined ways to control the actions of these engineered cells, to make them more effective at safely targeting cancer.

Developing CAR T cell therapy: blood cancers and beyond

In this short film, Dr Steve Lee, a Senior Research Fellow at the University of Birmingham, explains the science behind genetically reprogrammed T cells. How do they work, and what are the challenges to applying this type of therapy to a wider range of tumours?

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This video is from the free online course:

Cancer Immunotherapy: a Step Change in Cancer Treatment

University of Birmingham