Antibody-drug compounds and immunotherapy to treat breast cancer

November 25, 2015

To more efficiently treat breast cancer, scientists have been researching molecules that selectively bind to cancer cells and deliver a substance that can kill the tumor cells, for several years. Researchers from the University and University Hospital Basel have now for the first time successfully combined such an antibody-drug conjugate with a therapy that stimulates the immune system to attack tumor cells. This opens the door to new therapeutic options in the treatment of breast cancer, report the researchers in the scientific journal Science Translational Medicine.

In nearly every fifth breast cancer patient, an above-average number of HER2 receptors are located on the surface of the tumor cells. These receptors are molecules that send growth factor signals into the cell. The overabundance of receptors causes the cancer cells to divide rapidly and the tumor grows faster than average.

For some years now, a new class of drugs called antibody-drug conjugates (ADCs) have been used, which work in two ways: they consist of an antibody that binds selectively to the tumor cell receptor and interrupts the signal to propagate; they also act as a transport vehicle for a chemical substance that enters the cancer cells with the antibody and triggers their death. The researchers demonstrate that the use of specific cytotoxic substances can also have a beneficial effect on the body's immune system.

Combination with immunotherapy

Researchers, led by Prof. Alfred Zippelius at the Department of Biomedicine, from the University and University Hospital Basel have now gone one step further: in a pre-clinical study performed in mouse breast cancer models, they combined the ADC 'trastuzumab emtansine' with an additional immunotherapy that activates the immune system into attacking tumors more efficiently.

They focused on what is known as immunoregulatory checkpoints. These are receptors on immune cells, which control for example effector T-cells by dampening their activation if damage to healthy cells is imminent. By administering a complementary antibody, they blocked the function of two such immune checkpoints, whereby different types of endogenous T-cells were activated.

On its own, this immune response had no immediate effect in the fight against the utilized breast tumors, but in combination with the ADC it proved itself effective in attacking cancer cells in mice, resulting in the complete cure of the majority of mice receiving the combination therapy. The researchers were also able to further demonstrate that regulatory T-cells play a host protective role in this therapeutic setting. Their removal resulted in excessive inflammation and tissue damage.

"Our results clearly demonstrate that antibody-drug conjugates are suitable for use in a combination therapy, opening new perspectives for the treatment of breast cancer," says lead author Dr. Philipp Müller on the significance of the study.
-end-


University of Basel

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.