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NIH study advances personalized immunotherapy for metastatic breast cancer

An experimental form of immunotherapy that uses an individual’s own tumor-fighting immune cells could potentially be used to treat people with metastatic breast cancer, according to results from an ongoing clinical trial by Center researchers. National Cancer Institute (NCI) Cancer Research Center. , which is part of the National Institutes of Health. 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 (TIL ).

In a clinical trial involving 42 women with metastatic breast cancer, 28 (or 67%) generated an immune response against their cancer. The approach was used to treat six women, half of whom experienced measurable tumor shrinkage. The results of the trial were published on February 1, 2022 in the Journal of Clinical Oncology(link is external).

“It is popular dogma that hormone receptor positive breast cancers are not able to elicit an immune response and are not responsive to immunotherapy,” said study leader Steven A. Rosenberg, MD. , Ph.D., Chief of the NCI Center’s Surgery Branch. for cancer research. “The results suggest that this form of immunotherapy can be used to treat some people with metastatic breast cancer who have exhausted all other treatment options.”

Prior to TIL therapy, a woman with breast cancer had metastatic lesions in the chest wall (top left) and liver (bottom left). After receiving the immunotherapy her tumors shrunk completely and recent scans (right) show she is cancer free more than five years later.National Cancer Institute

Immunotherapy is a treatment that helps a person’s immune system fight cancer. However, most available immunotherapies, such as immune checkpoint inhibitors, have shown limited efficacy against hormone receptor positive breast cancers, which make up the majority of breast cancers.

The immunotherapy approach used in the trial was pioneered in the late 1980s by Dr. Rosenberg and colleagues at NCI. It relies on TILs, T cells that are found in and around the tumor.

TILs can target tumor cells that have specific proteins on their surface, called neoantigens, that immune cells recognize. Neoantigens are produced when mutations occur in tumor DNA. Other forms of immunotherapy have proven effective in the treatment of cancers, such as melanoma, which have many mutations, and therefore many neo-antigens. Its effectiveness in cancers that have fewer neoantigens, such as breast cancer, has been less clear, however.

The results of the new study come from an ongoing Phase 2 clinical trial led by Dr. Rosenberg and colleagues. This trial was designed to see if the immunotherapy approach could lead to tumor regressions in people with metastatic epithelial cancers, including breast cancer. In 2018, researchers showed that a woman with metastatic breast cancer who was treated in this trial had complete tumor shrinkage, known as complete response.

In the trial, researchers used whole genome sequencing to identify mutations in tumor samples from 42 women with metastatic breast cancer whose cancers had progressed despite all other treatments. The researchers then isolated the TILs from the tumor samples and, in laboratory tests, tested their reactivity against the neoantigens produced by the different tumor mutations.

Twenty-eight women had TILs that recognized at least one neoantigen. Almost all identified neoantigens were unique to each patient.

“It’s fascinating that the Achilles’ heel of these cancers could potentially be the very genetic mutations that caused the cancer,” Dr. Rosenberg said. “Since that 2018 study, we now have information on 42 patients, showing that the majority cause immune reactions.”

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

After the treatment, the tumors 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 52% and 69% tumor shrinkage after six months and 10 months, respectively. However, some diseases returned and were surgically removed. These 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 uncertainty about its influence on TIL therapy outcomes. However, they said, treatment with such checkpoint inhibitors alone did not lead to sustained tumor shrinkage in people with hormone receptor-positive metastatic breast cancer.

Dr. Rosenberg said that with the NCI’s new Cell Therapies Building scheduled to open early this year, he and his colleagues can begin to treat more people with metastatic breast cancer as part of the ongoing clinical trial. He noted that this new immunotherapy approach could also be used for people with other types of cancer.

“We use a patient’s own lymphocytes as a drug to treat cancer by targeting the unique mutations in that cancer,” he said. “This is a highly personalized treatment.”

About the Cancer Research Center (CCR): The CCR includes nearly 250 teams conducting basic, translational, and clinical research through the NCI’s Intramural Program – an environment supporting innovative science aimed at improving human health. The CCR clinical program is housed at the NIH Clinical Center, the world’s largest hospital dedicated to clinical research. For more information about CCR and its programs, visit ccr.cancer.gov.

About the National Cancer Institute (NCI): The NCI leads the National Cancer Program and NIH efforts to dramatically reduce cancer prevalence and improve the lives of cancer patients and their families through research in cancer prevention and biology, the development of new interventions and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call the NCI contact center, the Cancer Information Service, at 1-800-4-CANCER ( 1-800-422-6237).

About the National Institutes of Health (NIH): The NIH, the country’s medical research agency, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.



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