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

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 mutations 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 treatment 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 tumor-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 metastatic breast cancer 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 patients 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 cancer."

Nikolaos Zacharakis, Harshini Chinnasamy, Mary Black, Hui Xu, Yong-Chen Lu, Zhili Zheng, Anna Pasetto, Michelle Langhan, Thomas Shelton, Todd Prickett, Jared Gartner, Li Jia, Katarzyna Trebska-McGowan, Robert P Somerville, Paul F Robbins, Steven A Rosenberg, Stephanie L Goff, Steven A Feldman.
Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer.
Nature Medicine, volume 24, pages724-730 (2018). doi: 10.1038/s41591-018-0040-8.

Most Popular Now

Amgen and the Amgen Foundation commit up to $12.5 …

Amgen (NASDAQ:AMGN) and the Amgen Foundation announced an initial commitment of up to $12.5 million to support U.S. and global relief efforts to address critical needs in...

Novartis and life sciences companies commit expert…

Novartis and a consortium of life sciences companies announced an important collaboration to accelerate the development, manufacture and delivery of vaccines, diagnostics...

AstraZeneca to donate 9 million face masks to supp…

AstraZeneca is donating nine million face masks to support healthcare workers around the world as they respond to the COVID-19 (novel coronavirus) global pandemic. AstraZ...

Roche response to COVID-19 pandemic

Roche Group (SIX: RO, ROG; OTCQX: RHHBY), provided an update on the various actions the company is taking to address the COVID-19 pandemic. On March 19, 2020, Roche co...

Singapore modelling study estimates impact of phys…

A new modelling study conducted in a simulated Singapore setting has estimated that a combined approach of physical distancing [2] interventions, comprising quarantine (f...

CAR macrophages go beyond T cells to fight solid t…

Chimeric antigen receptor (CAR) T cell therapy has been a game-changer for blood cancers but has faced challenges in targeting solid tumors. Now researchers from the Pere...

FDA approves first plasma therapy for Houston Meth…

Houston Methodist received FDA approval Saturday to become the first academic medical center in the nation to transfuse donated plasma from a recovered COVID-19 patient i...

Consignment of 30 million hydroxychloroquine table…

Novartis announced that Sandoz, its generics and biosimilars division, has started to ship a consignment of 30 million doses of hydroxychloroquine tablets to the US Depar...

Experimental AI tool predicts which COVID-19 patie…

An artificial intelligence tool accurately predicted which patients newly infected with the COVID-19 virus would go on to develop severe respiratory disease, a new study ...

Vivli to launch a portal for sharing data from COV…

In a visible sign of data sharing leadership, Vivli, the Center for Clinical Research Data has committed to serving the open science community through the launch of a COV...

Roche initiates Phase III clinical trial of Actemr…

Roche (SIX: RO, ROG; OTCQX: RHHBY) is working with the Food & Drug Administration (FDA) to initiate a randomised, double-blind, placebo-controlled Phase III clinical tria...

Novartis commits to donate up to 130 million doses…

Novartis announced its commitment to donate up to 130 million doses of generic hydroxychloroquine to support the global COVID-19 pandemic response. Hydroxychloroquine and...