New Form of Immunotherapy Could Help Immune Cells Fight Breast Cancer

An experimental form of immunotherapy that uses an individual’s own tumor-fighting immune cells could potentially be used to treat individuals with metastatic breast cancer, according to results from an ongoing trial led by investigators at the Center for Cancer Research at the National Cancer Institute (NCI).

Many individuals with metastatic breast cancer can mount an immune reaction against their tumors, a prerequisite for this type of immunotherapy, which relies on tumor-infiltrating lymphocytes (TILs), the results from the trial, which were published Journal of Clinical Oncology, show.

In the clinical trial of 42 women with metastatic breast cancer, 28, or 67%, generated an immune reaction against their cancer.

The approach was used to treat 6 women, where half experienced measurable tumor shrinkage.“It’s popular dogma that hormone receptor–positive breast cancers are not capable of provoking an immune response and are not susceptible to immunotherapy,” Steven Rosenberg, MD, PhD, chief of the surgery branch at the Center for Cancer Research, said in a statement. “The findings suggest that this form of immunotherapy can be used to treat some people with metastatic breast cancer who have exhausted all other treatment options.”.

Most available immunotherapies, such as immune checkpoint inhibitors, have shown limited effectiveness against hormone receptor–positive breast cancers, which is the majority of breast cancers.

TILs can target tumor cells that have specific proteins on their surface that the immune cells recognize.

These proteins, called neoantigens, are produced when mutations occur in tumor DNA. Other forms of immunotherapy have been found effective in treating cancers, such as melanoma, because they have many mutations, which means they have more neoantigens.

The effectiveness in cancers with less neoantigens, such as breast cancer, has been less clear.

Investigators designed this trial to see if the immunotherapy approach could lead to tumor regressions in individuals with metastatic epithelial cancers, including breast cancer.

In 2018, investigators reported that 1 individual with metastatic breast cancer who was treated in this trial had complete tumor shrinkage, which is known as a complete response.

In the trial, whole-genome sequencing was used to identify mutations in tumor samples from the individuals with metastatic breast cancer whose cancer had progressed despite all other treatments.

Investigators isolated TILs from the tumor samples and tested their reactivity against neoantigens produced by different mutations in the tumor.

The findings showed that 28 women had TILs that recognized at least 1 neoantigen. Nearly all neoantigens identified were unique to each individual.

For 6 of these individuals who were treated, investigators took the reactive TILs and grew them to large numbers in the laboratory. They returned the immune cells to each individual via intravenous infusion.

All individuals were also given 4 doses of the immune checkpoint inhibitor, pembrolizumab (Keytruda, Merck) before the infusion to prevent newly introduced T cells from becoming inactivated.

After the treatment, the tumors shank in 3 of the 6 individuals. One individual remains cancer free, and the other 2 individuals had tumor shrinkage of about 52% and 69% after 6 months and 10 months, respectively.

However, some of the disease returned and had to be surgically removed.

The 2 women have no evidence of cancer approximately 5 and 3.5 years, respectively, after their TIL treatment.

The investigators 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 the TIL therapy.

However, treatment with the checkpoint inhibitors alone has not led to sustained tumor shrinkage in individuals with hormone receptor–positive metastatic breast cancer, investigators said.

Reference

NIH study advances personalized immunotherapy for metastatic breast cancer. EurekAlert. News release. February 1, 2022. Accessed February 2, 2022. https://www.eurekalert.org/news-releases/941686