Tuesday, 5 June 2018

Doctors hail world first as woman’s advanced breast cancer is eradicated - Immune-System Therapy Eradicated Breast Cancer in New Breakthrough

Photographer: Saul Loeb/AFP/Getty Images

Michelle Cortez
June 4, 2018, 11:00 PM GMT+8 Updated on June 4, 2018, 11:32 PM GMT+8

Gilead Sciences has licensed therapy; shares of company gain

Therapy leverages immune system cells found in patient tumors

An experimental therapy that extracts and multiplies powerful immune-system cells from inside tumors eradicated a patient’s breast cancer, a scientific first that could lead to new ways of treating malignancies that have resisted all other efforts.

Researchers at the U.S. National Cancer Institute gave the experimental treatment, which has since been licensed to Gilead Sciences Inc., to a 49-year-old woman whose cancer came roaring back after a decade in remission. The woman had tennis-ball-sized tumors in her liver and growing through her chest wall. Despite seven types of chemotherapy and hormonal therapy, her disease was still growing.

Ian Sample and Jessica Glenza

Mon 4 Jun 2018 16.00 BSTLast modified on Tue 5 Jun 2018 00.55 BST

A leading cancer researcher said the experiment was proof that we are on the ‘cusp of a major revolution’ in being able to target cancer with immunotherapy. Photograph: ilbusca/Getty Images

A woman with advanced breast cancer which had spread around her body has been completely cleared of the disease by a groundbreaking therapy that harnessed the power of her immune system to fight the tumours.

It is the first time that a patient with late-stage breast cancer has been successfully treated by a form of immunotherapy that uses the patient’s own immune cells to find and destroy cancer cells that have formed in the body.

Judy Perkins, an engineer from Florida, was 49 when she was selected for the radical new therapy after several rounds of routine chemotherapy failed to stop a tumour in her right breast from growing and spreading to her liver and other areas. At the time, she was given three years to live.

Doctors who cared for the woman at the US National Cancer Institute in Maryland said Perkins’s response had been “remarkable”: the therapy wiped out cancer cells so effectively that she has now been free of the disease for two years.

“My condition deteriorated a lot towards the end, and I had a tumour pressing on a nerve, which meant I spent my time trying not to move at all to avoid pain shooting down my arm. I had given up fighting,” Perkins said. “After the treatment dissolved most of my tumours, I was able to go for a 40-mile hike.”

Laszlo Radvanyi, scientific director of the Ontario Institute for Cancer Research, who was not involved in Perkins’s treatment, said it was “an unprecedented response in such advanced breast cancer.”
FacebookTwitterPinterest Judy Perkins says her condition had deteriorated a lot and she was planning her death. But since the treatment she has been on a 40 mile hike. Photograph: Courtesy of Judy Perkins

The dramatic success has raised hopes that the therapy will work in more patients with advanced breast cancer and other difficult to treat cancers, such as ovarian and prostate. Researchers are now planning full scale clinical trials to assess how effective the treatment could be.

“We are now at the cusp of a major revolution in finally realising the elusive goal of being able to target the plethora of mutations in cancer through immunotherapy,” Radvanyi said.

But experts caution that the treatment has only proved itself in one woman and that the clinical trials are needed to see how effective the therapy could be in other cancer patients. Researchers point out that while the treatment could in principle work for many different kinds of cancer, it will not help everyone.

To create the treatment, doctors first cut small pieces of tissue from Perkins’s tumours and studied the DNA to find mutations specific to her cancer. They focused on mutations that disrupted four genes which produced an array of abnormal proteins in the tumours.

Next, the doctors extracted immune cells known as tumour infiltrating lymphocytes, or TILs, from the tumour biopsies. These are cells from the patient’s immune system that have invaded the tumour in a bid to kill it, but which failed in the task by being either too weak or too few in number.

 Immune-System Therapy Eradicated Breast Cancer in New Breakthrough

After growing billions of these immune cells in the lab, the researchers screened them to find which ones would most effectively find and destroy the woman’s cancer cells by recognising their abnormal proteins.

The doctors treated Perkins by injecting 80 billion of the carefully-selected immune cells into her body. The therapy was given alongside pembrolizumab, a standard drug that can help the immune system to attack cancers. Tests after 42 weeks showed Perkins was completely cancer free. She has remained so ever since.

“It feels miraculous, and I am beyond amazed that I have now been free of cancer for two years,” Perkins said.

“I had resigned my job and was planning on dying. I had a bucket-list of things I needed to do before the end, like going to the Grand Canyon,” she added. “Now, I have gone back to normal everyday life.”

While the US doctors who developed the therapy cannot be sure how much the infused immune cells contributed to her recovery, the use of pembrolizumab alone has not been very effective for advanced breast cancer in the past. The infused T cells were found in Perkins’s system for at least 17 months after her treatment began.

The success, reported in the journal Nature Medicine, is all the more remarkable because breast cancers, like prostate and ovarian cancer, have relatively few mutations, which makes them harder for the immune system to spot amid the body’s healthy tissues.

Alan Melcher, professor of translational immunotherapy at the Institute of Cancer Research in London, who was not involved in the study said: “The work shows that even cancers like breast cancer, which don’t have many antigens, are amenable to this sort of treatment. It would certainly be applicable in principle to a range of tumours, and even those in which immunotherapy hasn’t worked so well yet.”

But Melcher points out that the therapy is complex and expensive and more importantly, requires doctors to find enough infiltrating immune cells in a patient’s tumour to make the treatment effective. “The case with other TIL therapies in the past is that they’ve not been able to expand enough T cells in many patients, there aren’t enough to start with.”

Simon Vincent, director of research at Breast Cancer Now, added: “This is a remarkable and extremely promising result, but we need to see this effect repeated in other patients before giving hope of a new immunotherapy for incurable metastatic breast cancer.

“Metastatic breast cancer remains incurable, and if we are to finally stop women dying we urgently need to find new ways to target and stop the spread of the disease. We are thrilled by this early finding, but we must remember that this type of immunotherapy remains an experimental approach that has a long way to go before it might be routinely available to patients.”

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Using a biopsy, researchers plucked rare cells custom-made by the immune system from inside tumors, but in numbers too small to help a patient on their own. They grew copies of the cells in the lab, multiplying them into billions over a period of weeks. They were then infused back into the patient.

Two-and-a-half years after getting the new cells, the woman is cancer-free. The method, while still in its infancy, also shrank hard-to-treat tumors in six other patients with colon and cervical cancers, said Steven Rosenberg, chief of surgery at the National Cancer Institute where it is being studied.

“They are attacking their own cancers,” Rosenberg said in an interview. “It’s as highly personalized as a treatment can be. We are creating a new drug for every patient, targeting the unique mutations in that same patient’s cancer.”

Gilead’s Kite unit signed a development agreement for the experimental therapy, Rosenberg said. The Foster City, California-based company is building out a pipeline of cancer drugs after years of success with treating viral infections such as hepatitis and HIV.

Gilead shares gained as much as 3.7 percent on Monday, and were up 1.9 percent to $69.60 at 11:16 a.m. in New York.

The results were published Monday in the scientific journal Nature Medicine.
Custom Therapy

So far, the researchers have treated 40 patients, all with types of tumors that account for 80 percent of cancer deaths, according to Rosenberg. Seven have responded to the therapy.

It took about eight weeks to craft the therapy for the breast-cancer patient. Six weeks after getting it, the amount of cancer in her body had shrunk by half. Two and a half years later, all signs of her cancer have disappeared.

The immunotherapy field has seen major breakthroughs in the past year, including the approval of two so-called CAR-T treatments from Gilead and Novartis AG that extract T-cells from a patient’s blood and re-engineer them to recognize malignancies. Drugmakers have had less success using that technique on widespread solid tumors.
Inside the Tumor

Rosenberg’s team takes a different tack. The researchers isolate rare T-cells that each patient produces in response to unique mutations that fuel the development of their cancer. Minute amounts of these natural T-cells infiltrate the tumor, though they aren’t present in high enough quantities to combat the growing cancer, Rosenberg said.

After extracting the tumor-infiltrating lymphocytes from a biopsy, his team can multiply the cells and give billions of them back to the patient.

The group is getting better at identifying the rare T-cells that can attack the tumor, finding three times more of them in samples than they were even three months ago, Rosenberg said. There is still a long way to go, he said, but it’s an approach that isn’t specific to a certain cancer type, meaning it could evolve into an effective therapy for many forms of the disease, he said.

“Part of the excitement is because all cancers contain mutations, it’s a technique that could potentially be applied to any tumor type,” Rosenberg said. “It opens the door to the treatment of almost any cancer.”
(Updates with Gilead shares in seventh paragraph.)

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