Healthcare (Commonwealth Union) – Scientists have formed a new antibody-based approach that can curb the growth of breast cancers that no longer respond to standard treatments.
The breakthrough from King’s College London — released recently — could open up fresh options for tackling some of the most aggressive breast cancers. It may be especially valuable for patients whose disease has stopped responding to current drugs, as well as for those with triple-negative breast cancer — a form that lacks the receptors most therapies target, leaving few treatment choices.
The scientists engineered an antibody that not only directly attacks tumour cells but also recruits the body’s immune system to join the fight. This “triple-modified” antibody is the first of its type: one end binds to the cancer cell while the other engages immune cells.
Although antibodies have been engineered before to better trigger immune activity, powerful candidates suitable for breast cancer treatment are still in short supply. The Breast Cancer Now Research Unit at King’s College London has led work in this area for over ten years, concentrating on analysing patients’ immune responses and creating novel antibodies designed to activate those defences.
In the new study, tests in the lab and in animal models showed that the engineered antibody attached to immune cells far more tightly than existing therapies. This, in turn, switched on the tumour-infiltrating immune cells and prompted them to attack the cancer, slowing the growth of both triple-negative and drug-resistant breast tumours.
The team also discovered that the redesigned antibody stimulated immune cells travelling in the blood, potentially improving the body’s overall ability to spot and destroy cancer.
Lead author Dr Alicia Chenoweth from the Faculty of Life Sciences & Medicine at King’s College London pointed out that by making a handful of targeted alterations to the antibody’s structure, they saw that it could trigger the immune system much more strongly than an unmodified antibody currently used to treat breast cancer.
She further indicated that a majority of the immune cells within the breast tumours are in a ‘suppressed’ state, which is hard to activate using unmodified antibodies and they discovered their triple-engineered antibodies did not just have the ability to activate these immune cells to destoy the cancer cells, but shifted these immune cells to aa increased ‘activated’ state in general.
The lead author Professor Sophia Karagiannis, who is an expert in Translational Cancer Immunology and Immunotherapy for the King’s College London, is the lead of the study. She indicated that by looking into key immune cell receptors in breast tumours, that consisted of those tumours resistant to chemotherapy and immunotherapy, they have designed the antibody to make them improve their engagement and harness the immune system in a way that has not been done or tested in cancer on prior occasions.
“If it proves successful, it could stimulate the immune system directly and address the significant unmet need we see in treatment resistant cancers including triple-negative breast cancer.”
Triple-negative breast cancer makes up about 15% of all breast cancer cases. This form of the disease does not have receptors for the hormone’s estrogen or progesterone, nor does it express the HER2 protein — all of which are common drug targets in many other breast cancer types. Because these receptors are absent, hormone-based therapies and HER2-directed drugs do not work for this subgroup, leaving patients with limited treatment choices and a greater likelihood of the cancer returning.
HER2-positive tumours are typically managed with targeted medicines, which have significantly improved survival for many people. However, in some cases the cancer eventually stops responding, and this treatment resistance remains a major hurdle in clinical care.
Dr Simon Vincent, who is the chief scientific officer at Breast Cancer Now, explains “This promising, early-stage research offers hope for more and better treatments for over 8,000 women who are diagnosed with triple negative breast cancer each year in the UK.
