New approach to immunotherapy leads to complete response in breast cancer patient

June 4, 2018, National Cancer Institute
Three-dimensional culture of human breast cancer cells, with DNA stained blue and a protein in the cell surface membrane stained green. Image created in 2014 by Tom Misteli, Ph.D., and Karen Meaburn, Ph.D. at the NIH IRP.

A novel approach to immunotherapy developed by researchers at the National Cancer Institute (NCI) has led to the complete regression of breast cancer in a patient who was unresponsive to all other treatments. This patient received the treatment in a clinical trial led by Steven A. Rosenberg, M.D., Ph.D., chief of the Surgery Branch at NCI's Center for Cancer Research (CCR), and the findings were published June 4, 2018 in Nature Medicine. NCI is part of the National Institutes of Health.

"We've developed a high-throughput method to identify present in a cancer that are recognized by the immune system," Dr. Rosenberg said. "This research is experimental right now. But because this new approach to immunotherapy is dependent on mutations, not on cancer type, it is in a sense a blueprint we can use for the of many types of cancer."

The new immunotherapy approach is a modified form of adoptive cell transfer (ACT). ACT has been effective in treating melanoma, which has high levels of somatic, or acquired, mutations. However, it has been less effective with some common epithelial cancers, or cancers that start in the lining of organs, that have lower levels of mutations, such as stomach, esophageal, ovarian, and breast cancers.

In an ongoing phase 2 clinical trial, the investigators are developing a form of ACT that uses -infiltrating lymphocytes (TILs) that specifically target tumor cell mutations to see if they can shrink tumors in patients with these common epithelial cancers. As with other forms of ACT, the selected TILs are grown to large numbers in the laboratory and are then infused back into the patient (who has in the meantime undergone treatment to deplete remaining lymphocytes) to create a stronger immune response against the tumor.

A patient with came to the trial after receiving multiple treatments, including several chemotherapy and hormonal treatments, that had not stopped her cancer from progressing. To treat her, the researchers sequenced DNA and RNA from one of her tumors, as well as normal tissue to see which mutations were unique to her cancer, and identified 62 different mutations in her tumor cells.

The researchers then tested different TILs from the patient to find those that recognized one or more of these mutated proteins. TILs recognized four of the mutant proteins, and the TILs then were expanded and infused back into the patient. She was also given the checkpoint inhibitor pembrolizumab to prevent the possible inactivation of the infused T cells by factors in the tumor microenvironment. After the treatment, all of this patient's cancer disappeared and has not returned more than 22 months later.

"This is an illustrative case report that highlights, once again, the power of immunotherapy," said Tom Misteli, Ph.D., director of CCR at NCI. "If confirmed in a larger study, it promises to further extend the reach of this T-cell therapy to a broader spectrum of cancers."

Investigators have seen similar results using mutation-targeted TIL treatment for patients in the same trial with other epithelial cancers, including liver cancer and colorectal cancer. Dr. Rosenberg explained that results like this in with solid epithelial tumors are important because ACT has not been as successful with these kinds of cancers as with other types that have more mutations.

He said the "big picture" here is this kind of treatment is not cancer-type specific. "All cancers have mutations, and that's what we're attacking with this immunotherapy," he said. "It is ironic that the very mutations that cause the cancer may prove to be the best targets to treat the ."

Explore further: Study extends potential for personalized immunotherapy to large variety of cancers

More information: Nikolaos Zacharakis et al, Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer, Nature Medicine (2018). DOI: 10.1038/s41591-018-0040-8

Related Stories

Study extends potential for personalized immunotherapy to large variety of cancers

March 16, 2018
A Ludwig Cancer Research study shows that ovarian cancer, which has proved resistant to currently available immunotherapies, could be susceptible to personalized immunotherapy. Led by Alexandre Harari and George Coukos, director ...

New approach identifies cancer mutations as targets of effective melanoma immunotherapy

July 1, 2014
A new approach demonstrated that the recognition of unique cancer mutations appeared to be responsible for complete cancer regressions in two metastatic melanoma patients treated with a type of immunotherapy called adoptive ...

Cellular immunotherapy targets a common human cancer mutation

December 7, 2016
In a study of an immune therapy for colorectal cancer that involved a single patient, a team of researchers at the National Cancer Institute (NCI) identified a method for targeting the cancer-causing protein produced by a ...

Preclinical study suggests ARID1a may be useful biomarker for immunotherapy

May 7, 2018
Functional loss of ARID1a, a frequently mutated tumor suppressor gene, causes deficiencies in normal DNA repair and may sensitize tumors to immune checkpoint blockade therapies, according to researchers from The University ...

Research discovers how some cancers resist treatment

March 23, 2018
An international team of researchers led by Lucio Miele, MD, PhD, Professor and Chair of Genetics at LSU Health New Orleans School of Medicine, and Justin Stebbing, BM BCh MA, PhD, Professor of Cancer Medicine and Medical ...

Two immunotherapies used together for the first time to tackle tumors

March 26, 2018
Two immunotherapies - one that enables the T-cells a patient already has to better attack a tumor and another that can produce an independent and vigorous immune response - are being given together for the first time to help ...

Recommended for you

10-year follow-up after negative colonoscopies linked to lower colorectal cancer risk

December 17, 2018
Ten years after a negative colonoscopy, Kaiser Permanente members had 46 percent lower risk of being diagnosed with and were 88 percent less likely to die from colorectal cancer compared with those who did not undergo colorectal ...

Survivors of childhood Hodgkin lymphoma face high long-term risk of solid cancers

December 17, 2018
New research refines existing evidence that survivors of childhood Hodgkin lymphoma face an elevated risk of developing various types of solid tumors many years later. In addition, certain subgroups of patients have an especially ...

Immunotherapy combo not approved for advanced kidney cancer patients on the NHS

December 14, 2018
People with a certain type of advanced kidney cancer will not be able to have a combination of two immunotherapy drugs on the NHS in England.

New drug seeks receptors in sarcoma cells, attacks tumors in animal trials

December 13, 2018
A new compound that targets a receptor within sarcoma cancer cells shrank tumors and hampered their ability to spread in mice and pigs, a study from researchers at the University of Illinois reports.

Surgery unnecessary for many prostate cancer patients

December 13, 2018
Otherwise healthy men with advanced prostate cancer may benefit greatly from surgery, but many with this diagnosis have no need for it. These conclusions were reached by researchers after following a large group of Scandinavian ...

Lethal combination: Drug cocktail turns off the juice to cancer cells

December 12, 2018
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth—this was discovered by researchers from the University of Basel's Biozentrum two years ago. In a follow-up study, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.