Utilizing Th1 to Prevent HER2-Positive Disease Recurrence

January 7, 2016

While there are several great treatment options that specifically target HER2, many patients experience recurrence after treatment. This may be due to cancer-induced weakness in the patient's immune system.

HER2-positive breast cancer cells contain a protein called human epidermal growth factor receptor 2 (HER2). When a mutation is present in the HER2 gene, excess HER2 protein is produced and in turn, causes the growth of cancer cells. This mutation is responsible for one out of every five breast cancers.

While there are several great treatment options that specifically target HER2, many patients experience recurrence after treatment. This may be due to cancer-induced weakness in the patient's immune system.

To address this risk of recurrence, researchers from the Perelman School of Medicine at the University of Pennsylvania studied this issue and identified a cancer-induced weakness in the patient’s immune system-an area where an HER2-targeted vaccine could be developed.

“We know that it’s not a fixed immune defect, because we have several clinical trials open where we’re vaccinating people and can restore anti-HER2 responsivity,” said the study’s senior author Brian J. Czerniecki, MD, PhD, the Rhodes-Harrington Professor in Surgical Oncology at Penn and co-director of the Rena Rowan Breast Center at Penn’s Abramson Cancer Center, in a Penn news release. Their research has focused on the T-helper type 1, or Th1, immune response in cancer, in which “helper” T cells mobilize killer cells to attack cancer-related targets.

Dr. Czerniecki and his research team found that T cells from patients whose breast cancer had recently recurred showed weaker response to the HER2 receptor protein, compared to T cells from patients whose breast cancer had not recurred over a long period following treatment. This was first published in the journal JAMA Oncology in December 2015.

The Penn researchers isolated immune cells from 95 women with invasive HER2-positive breast cancer, and analyzed the cells’ ability to mount a Th1 response against the HER2 growth factor receptor protein. The cells from women with recently recurrent cancer that had not had additional treatment had approximately one-tenth of the anti-HER2 response compared with women whose HER2-positive breast cancer had not recurred for at least 2 years following treatment.

It isn't clear how patients lose their anti-HER2 responsivity during HER2 tumor formation, but researchers continue to study the mechanism. In the meantime, an HER2-targeted vaccine may be the answer.

Looking toward the future, patients diagnosed with HER2-positive breast cancer may undergo immune status monitoring with blood tests before, during, and after treatment to enable oncologists to gauge the risk of recurrence, and possibly to reduce that risk with therapies that boost anti-HER2 immunity.