This website is intended for healthcare professionals only.
Take a look at a selection of our recent media coverage:
18th August 2021
The treatment of cancer has traditionally involved surgery, chemotherapy or radiotherapy although in recent years, there has been increased interest in immunotherapy which makes use of the patient’s immune system to fight cancer. One form of immunotherapy is Chimeric Antigen Receptor (CAR) T-cell therapy which involves genetic modification of a patient’s T cells to express a specific tumour antigen. After modification, these modified T cells are infused back into a patient, attacking and destroying chemotherapy-resistant cancer. However, a major limitation to the use of CAR-T cells is that the tumour antigen can also be expressed by normal, healthy tissue and the modified T cells are unable to differentiate between malignant and benign cells. It is therefore not always easy to identify a specific antigen that is preferentially expressed on tumour cells. This led a team from the Department of Bioengineering, University of California, US, to create inducible cells that were engineered to express the surface protein but only in response to short-pulsed, focused ultrasound stimulation.
The team subcutaneously injected the specific CAR-T cells at the site of a tumour in mice, followed by three 5-minute pulses of focused ultrasound at 43 degrees centigrade. This resulted in a significant reduction in tumour size. To ensure that it was specifically the combination of the CAR-T cells and focused ultrasound that were shrinking the tumour, the team used two control groups of mice with tumours. In one group, the pulsed ultrasound was used in the absence of the specific CAR-T cells injected and this had no impact on tumour growth. The second group of mice also received the ultrasound but this time, but this time in the presence of naïve T cells, as opposed to the CAR-T cells and again, there was no effect on tumour growth. Finally, the researchers examined whether localised, pulsed ultrasound was effective using mice with both a local and distal tumour. Injection of standard CAR-T cells reduced the size of both the local and distal tumour. However, after injection of the CAR-T cells and directing the ultrasound only at the local tumour, there was a dramatic reduction in size of the local, but not distal tumour.
Discussing their findings, the authors noted the use of the targeted pulsed ultrasound was a potentially effective approach to the treatment of localised tumours. They added the local administration of the CAR-T cells has already been tested in animals and patients and a further advantage of their technique was the potential for a reduction in off-target activity, i.e., where the CAR-T cells affected healthy tissue.
While this novel approach appeared to be effective, further work is required to ensure that the method represents a much safer form of cell therapy.
Wu Y et al. Control of the activity of CAR-T cells within tumours via focused ultrasound. Nat Biomed Eng 2021
9th July 2021
Breast cancer is the most common cancer in women worldwide and in 2020, there were 2.2 million cases and nearly 685,000 deaths. Breast cancer is a heterogenous disease with various types and different sensitivities to treatment, e.g., oestrogen receptor (ER) positive, progesterone receptor (PR) positive and hormone receptor (HR) negative. Among those with ER positive tumours, treatment with adjunctive therapy such as tamoxifen for five years is recommended. Nevertheless, even after treatment with tamoxifen, breast cancer can return over the intervening years, metastasise and lead to death. The use of clinical breast cancer markers such as tumour size or grade can be used to provide estimates of survival for up to 10 years and both increased tumour size and grade are associated with a reduced short-term survival. However, what is far less clear, is whether any of these markers are associated with longer term survival.
Given that both ER-positive and ERBB2-negative (i.e., HER2) disease are associated with a continuous risk of recurrent disease after the primary diagnosis, a team from the Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden, sought to determine whether both clinically used markers and treatment with tamoxifen were associated with long-term survival in patients with breast cancer. The team turned to data from the Stockholm tamoxifen (STO-3) trial, which enrolled postmenopausal women with lymph-node negative breast cancer and tumours less than 30mm in diameter, between 1976 and 1990 and who were randomised to tamoxifen 40mg daily or no endocrine therapy. In 1983, women with no recurrence after 2 years on tamoxifen, were given the drug for a further 3 years. The team undertook an analysis of tissue samples that were available from patients in the study. The tumour grade (1 to 3) had been assessed in 2014 by a pathologist and tumour size was categorised as T1a/b if 10mm or less, T1c if 11–20mm and T2 if larger than 20mm. All patients had a unique national registration number and which was linked with a cancer registry, allowing the team to obtain long-term follow-up data after 25 years.
The sample contained 565 postmenopausal women with a mean age of 62 years. Just over half (52.2%) of tumours were graded as T1c and nearly a third (30%), T1a/b. Patients with T1a/b tumours had the best long-term survival (88%) compared to those with T1c tumours (76%) or T2 tumours (63%). Similarly, the highest level of survival (81%) occurred in those with grade 1 tumours compared with grade 3 tumours (65%). Using this data, the team estimated a 69% reduced risk of disease recurrence for those with T1a/b sized tumours (hazard ratio, HR = 0.31, 95% CI 0.17–55). In terms of treatment, those given tamoxifen with grade 1–2 tumours also experienced a significantly reduced risk of disease recurrence (HR = 0.24, 95% CI 0.07 – 0.82) compared with those who did receive the drug. However, use of tamoxifen also produced a significant survival benefit in those with T2 tumours (HR = 0.34).
The authors concluded that tumour size, followed by grade and use of tamoxifen were independently associated with long-term survival in breast cancer.
Dar H et al. Assessment of 25-Year Survival of Women with Oestrogen Receptor–Positive/ERBB2-Negative Breast Cancer Treated with and Without Tamoxifen Therapy. A Secondary Analysis of Data from the Stockholm Tamoxifen Randomised Clinical Trial. JAMA Netw Open 2021.