NIH study advances personalised immunotherapy for metastatic breast cancer

An experimental form of immunotherapy that uses an individual’s own tumour-fighting immune cells could potentially be used to treat people with metastatic breast cancer, according to results from an ongoing clinical trial led by researchers at the National Cancer Institute’s (NCI) Center for Cancer Research. Many people with metastatic breast cancer can mount an immune reaction against their tumours, the study found, a prerequisite for this type of immunotherapy, which relies on what are called Tumour-Infiltrating Lymphocytes (TILs), a statement from NIH said.

The statement also said that in a clinical trial of 42 women with metastatic breast cancer, 28 (or 67 per cent) generated an immune reaction against their cancer. The approach was used to treat six women, half of whom experienced measurable tumour shrinkage. Results from the trial appeared on 1st February, 2022, in the Journal of Clinical Oncology.

TILs can target tumour cells that have specific proteins on their surface, called neoantigens, that the immune cells recognise. Neoantigens are produced when mutations occur in tumour DNA. Other forms of immunotherapy have been found to be effective in treating cancers, such as melanoma, that have many mutations, and therefore many neoantigens. Its effectiveness in cancers that have fewer neoantigens, such as breast cancer, however, has been less clear, the statement further said.

The results of the new study come from an ongoing phase-II clinical trial. This trial was designed to see if the immunotherapy approach could lead to tumour regressions in people with metastatic epithelial cancers, including breast cancer. In 2018, the researchers showed that one woman with metastatic breast cancer who was treated in this trial had complete tumour shrinkage, known as a complete response, it added.

The statement also noted that in the trial, the researchers used whole-genome sequencing to identify mutations in tumour samples from 42 women with metastatic breast cancer whose cancers had progressed despite all other treatments. The researchers then isolated TILs from the tumour samples and, in lab tests, tested their reactivity against neoantigens produced by the different mutations in the tumour. Twenty-eight women had TILs that recognised at least one neoantigen. Nearly all the neoantigens identified were unique to each patient.

For the six women treated, the researchers took the reactive TILs and grew them to large numbers in the lab. They then returned the immune cells to each patient via intravenous infusion. All the patients were also given four doses of the immune checkpoint inhibitor pembrolizumab (Keytruda) before the infusion to prevent the newly introduced T cells from becoming inactivated, according to the statement.

Further, as per the statement, after the treatment, tumours shrank in three of the six women. One is the original woman reported in the 2018 study, who remains cancer-free to this day. The other two women had tumour shrinkage of 52 per cent and 69 per cent after six months and 10 months, respectively. However, some disease returned and was surgically removed. Those women now have no evidence of cancer approximately five years and 3.5 years, respectively, after their TIL treatment.

The researchers acknowledged that the use of pembrolizumab, which has been approved for some early-stage breast cancers, may raise uncertainties about its influence on the outcome of TIL therapy. However, they said, treatment with such checkpoint inhibitors alone has not led to sustained tumour shrinkage in people with hormone receptor-positive metastatic breast cancer, concluded the statement.