At the Breast Cancer Now Research Unit at Kings College London, scientists have developed ‘triple engineered’ antibodies that can restrict the growth of aggressive and treatment-resistant breast cancers.
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These first-of-their-kind antibodies not only attack the tumour cells directly but also harness the body’s own immune defences, according to new findings published in Cancer Research.
Professor Sophia Karagiannis and her team are now continuing to optimise the therapy with the hope that one day it can be tested in clinical trials.
Understanding antibody engineering
An antibody is a Y-shaped protein made by the immune system to recognise and bind to things that could be harmful, like viruses or bacteria. In some cases, antibodies can also attach to cancer cells and help to destroy them.
Each antibody has 2 binding sites, located at the 2 top ends of the Y-shape, which can attach directly to proteins on the cancer cell. The ‘tail’ or ‘stem’ of the Y-shaped antibody is then responsible for activating the immune system.
In this study, Sophia and her team developed first of their kind ‘triple engineered’ antibodies in the lab. This meant the researchers designed each of the 2 the antibody binding sites to bind to 2 different proteins found on the surface of more aggressive and treatment-resistant cancer cells. This includes triple negative and HER2-positive breast cancer cells. And the team also engineered the antibody ‘tail’ to improve its ability to launch an immune response against the cancer cells.
By examining key immune cell receptors in breast tumours, including those tumours resistant to chemotherapy and immunotherapy, we have designed our antibody to make them interact better and harness the immune system in a way that has never been done or tested in cancer before.
Professor Sophia Karagiannis
Strengthening the immune response
This means the antibody can latch directly onto cancer cells on one end and draw in immune cells on the other. This is important, because the environment around a tumour is usually set up in a way that makes it difficult for the immune system to attack.
The researchers also showed that these ‘triple engineered’ antibodies could launch a stronger immune response than currently available treatments in experiments in the lab and in mice. The antibodies activated the immune cells already present in the tumour to attack the cancer cells, limiting further tumour growth.
Many of the immune cells in breast tumours are in a ‘suppressed’ state, difficult to activate with unmodified antibodies. We found our triple-engineered antibodies were not only able to activate these immune cells to kill the cancer cells, but shifted these immune cells to a more ‘activated’ state overall.
Dr Alicia Chenoweth
Hope for future treatments
The team is now continuing this exciting work to optimise the therapy so that one day it can be tested in people living with breast cancer in clinical trials.
Triple negative breast cancer makes up around 15% of breast cancer cases diagnosed every year in the UK. It can be more aggressive and lacks the proteins that are the target of many current targeted breast cancer treatments. So, we need to find new ways to target this type of breast cancer.
For people living with HER2-positive breast cancers, targeted drugs like trastuzumab are available and can be very effective. But sometimes breast cancers can become resistant to these treatments, so it’s important to find new ways to target the disease.
This is early-stage research, but it offers hope of new, targeted treatments for aggressive and treatment-resistant breast cancers in the future.
The study was published in Cancer Research, a journal of the American Association for Cancer Research, and funded by Breast Cancer Now.
Tickled pink
Our research is only possible thanks to the incredible generosity of its supporters. This project’s funding was supported by the Asda Tickled Pink campaign.