Cancer: A Giant Step For Immunotherapy

A Food and Drug Administration (FDA) panel opened a new era in medicine, unanimously recommending that the agency approve the first-ever treatment that genetically alters a patient’s own cells to fight cancer, transforming them into what scientists call “a living drug” that powerfully bolsters the immune system to shut down the disease.

If the F.D.A. accepts the recommendation, which is likely, the treatment will be the first gene therapy ever to reach the market. Others are expected: Researchers and drug companies have been engaged in intense competition for decades to reach this milestone. Novartis is now poised to be the first. Its treatment is for a type of leukemia, and it is working on similar types of treatments in hundreds of patients for another form of the disease, as well as multiple myeloma and an aggressive brain tumor.

To use the technique, a separate treatment must be created for each patient — their cells removed at an approved medical center, frozen, shipped to a Novartis plant for thawing and processing, frozen again and shipped back to the treatment center.

A single dose of the resulting product has brought long remissions, and possibly cures, to scores of patients in studies who were facing death because every other treatment had failed. The panel recommended approving the treatment for B-cell acute lymphoblastic leukemia that has resisted treatment, or relapsed, in children and young adults aged 3 to 25.

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We believe that when this treatment is approved it will save thousands of children’s lives around the world,” Emily’s father, Tom Whitehead, told the panel. “I hope that someday all of you on the advisory committee can tell your families for generations that you were part of the process that ended the use of toxic treatments like chemotherapy and radiation as standard treatment, and turned blood cancers into a treatable disease that even after relapse most people survive.”

The main evidence that Novartis presented to the F.D.A. came from a study of 63 patients who received the treatment from April 2015 to August 2016. Fifty-two of them, or 82.5 percent, went into remission — a high rate for such a severe disease. Eleven others died.

It’s a new world, an exciting therapy,” said Dr. Gwen Nichols, the chief medical officer of the Leukemia and Lymphoma Society, which paid for some of the research that led to the treatment. The next step, she said, will be to determine “what we can combine it with and is there a way to use it in the future to treat patients with less disease, so that the immune system is in better shape and really able to fight.” She added, “This is the beginning of something big.”

Source: http://www.chop.edu/
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https://www.nytimes.com/

How To Boost Body’s Cancer Defenses

After radiation treatment, dying cancer cells spit out mutated proteins into the body. Scientists now know that immune system can detect these proteins and kill cancer in other parts of the body using these protein markers as a guide – a phenomenon that University of North Carolina Lineberger Comprehensive Cancer Center (UNC Lineberg) scientists are looking to harness to improve cancer treatment.

In the journal Nature Nanotechnology, the researchers report on strides made in the development of a strategy to improve the immune system’s detection of cancer proteins by using “stickynanoparticles called “antigen-capturing nanoparticles.” They believe these particles could work synergistically with immunotherapy drugs designed to boost the immune system’s response to cancer.

Our hypothesis was that if we use a nanoparticle to grab onto these cancer proteins, we’d probably get a more robust immune response to the cancer,” said the study’s senior author Andrew Z. Wang, MD, a UNC Lineberger member and associate professor in the UNC School of Medicine Department of Radiation Oncology. “We think it works because nanoparticles are attractive to the immune system. Immune cells don’t like anything that’s nano-sized; they think they are viruses, and will respond to them.”

Radiation therapy is commonly used to treat a wide array of cancers. Previously, doctors have observed a phenomenon they call the “abscopal effect,” in which a patient experiences tumor shrinkage outside of the primary site that was treated with radiation. This observation in a single patient with melanoma was reported in the New England Journal of Medicine in 2012.

Scientists believe this occurs because, after radiation, immune cells are recruited to the tumor site. Once they’ve arrived, these immune cells use mutated proteins released by dying cancer cells to train other immune cells to recognize and fight cancer elsewhere. This effect works synergistically with immunotherapy drugs called “checkpoint inhibitors,” which release the immune system’s brakes, thereby helping the body’s own defense system to attack the cancer.

Cancer cells discharge these mutated proteins – which become markers for the immune system — as a result of genetic mutations, said study co-author Jonathan Serody, MD, UNC Lineberger’s associate director for translational research.

The theory is that in cancer, tumors accumulate large numbers of mutations across their genomes, and those mutated genes can make mutant proteins, and any of those mutant proteins can be chopped up and presented to the immune system as a foreign,” said Serody, who is also the Elizabeth Thomas Professor in the UNC School of Medicine. “Your body is designed not to respond to its own proteins, but there’s no system that controls its response to new proteins, and you have a broad array of immune cells that could launch a response to them.

The UNC Lineberger researchers demonstrated in preclinical studies they could successfully design nanoparticles to capture mutated proteins released by tumors. Once these nanoparticles are taken up by immune cells, the tumor proteins attached to their surface can help immune cells recognize identify cancer cells across body.

Source: http://unclineberger.org/

Nanoparticles reprogram immune cells to fight cancer

Dr. Matthias Stephan has a bold vision. He imagines a future where patients with leukemia could be treated as early as the day they are diagnosed with cellular immunotherapy that’s available in their neighborhood clinic and is as simple to administer as today’s chemotherapy, but without the harsh side effects. The key to that scientific leap? Nanoparticles, tiny technology that’s able to carry tumor-targeting genes directly to immune cells still within the body and program them to destroy cancer. In a proof-of-principle study published Monday in Nature Nanotechnology, Stephan and other researchers at Fred Hutchinson Cancer Research Center showed that nanoparticle-programmed immune cells, known as T cells, can clear or slow the progression of leukemia in a preclinical model.

nanoparticles reprogram genes

“Our technology is the first that we know of to quickly program tumor-recognizing capabilities into T cells without extracting them for laboratory manipulation,” said Stephan, the study’s senior author. Although his method for programming T cells is still several steps away from the clinic, Stephan envisions a future in which biodegradable nanoparticles could transform cell-based immunotherapies — whether for cancer or infectious disease — into an easily administered, off-the-shelf treatment that’s available anywhere.

Stephan imagines that in the future, nanoparticle-based immunotherapy could be “something that is available right away and can hopefully out-compete chemotherapies. That’s my excitement.”

Source: https://www.fredhutch.org/

ImmunoTherapy Registers Success Against Brain Cancer

Using the immune system to beat cancer is quickly becoming a promising new strategy for battling tumors. But most of the success so far has been with blood cancers like lymphomas and leukemias. Immunotherapy, as it’s called, has yet to prove itself with solid tumors like breast, prostate, lung, colon and brain cancers.But in a report published in the New England Journal of Medicine, researchers led by Dr. Behnam Badie from the City of Hope Beckman Research Institute and Medical Center say that the same immune-based therapy that is successful against blood cancers also helped a patient with advanced brain cancer.

brain cancer

The 50-year-old man with glioblastoma, a particularly aggressive type of brain tumor, had already been treated with surgery, radiation and anti-tumor drug therapies. Despite these treatments, his cancer had returned and also spread to other parts of his brain and spinal cord. Badie and his team extracted immune cells from him, then engineered them to express proteins on their surface that would recognize and destroy glioblastoma tumor cells. After surgery to remove the bulk of the brain tumor, Badie and his colleagues directly injected the site with the modified immune cells (called chimeric antigen receptor T cells, or CAR T cells) six times, and the remaining part of this tumor stopped growing.

Other smaller growths in the brain continued to grow, however, so the patient received 10 more doses of the CAR T cells injected into the cavities in the brain, called the ventricles. This is the first time that immune cells have been injected into these brain regions, because introducing anything into the ventricles can cause dangerous and possibly deadly inflammation. The man did not develop such serious complications, however, and after about four months, these tumors too started to shrink. By six months, almost all had disappeared.

If the patient had not received the CAR T therapy, he likely would only have survived a few weeks after his cancer recurred, says Badie. But after being treated with the immune therapy, his cancer did not grow or recur for nearly eight months. “If we can do the same for other patients, that would be an amazing accomplishment that many decades of work and research on glioblastoma have never done,” says Badie, whose own father passed away a decade ago from glioblastoma.

Source: http://time.com/

Immunotherapy Could Eradicate A Third of All Cancers

In August 2015, former US President Jimmy Carter, then 91, announced he had cancer. The diagnosis was metastatic melanoma, and it had spread to his brain. He thought he had merely weeks to live. Just four months later, he made headlines again, revealing he had tested cancer-free. Before long, doctors said he no longer needed treatment. That remarkable turn came from a combination of a traditional therapy, radiation, and a new one, an immunotherapy drug called Keytruda, which was delivered intravenously once every three weeks. Keytruda had only been approved for about a year at that point.

Drug companies see potential for a new group of mega moneymakers. Investors and billionaires, like former New York Mayor Michael Bloomberg and Silicon Valley billionaire Sean Parker, have invested hundreds of millions into researching new treatments. New drugs such as Keytruda are a type of immunotherapy called checkpoint inhibitors. Most people have a type of protein that stops their immune systems from fighting the cancerous cells. Keytruda and similar drugs block those proteins. It’s like taking down a guard tower, allowing the body’s own immune system force to flood past a barrier, where it then gets to work killing and clearing away the cancer cellsCheckpoint inhibitors were first approved to treat melanoma but have since gone on to tackle lung cancer, bladder cancer, blood cancers, and other cancers.

Dan Chen, vice president and global head of cancer immunotherapy development at Genentech considers  checkpoint inhibitor Tecentriq to be the foundation of the company’s cancer immunotherapy program.

cancer-cells

This is a critical program for us. It allowed us to learn an enormous amount about cancer immunity,” like how the drugs work to inhibit the checkpoints, Chen said. Genentech points to patients like Bob Schoenbauer to show why the company is “investing more than ever to bring personalized cancer immunotherapy (PCI) to people with cancer.”

Schoenbauer had been diagnosed with late-stage inoperable lung cancer in 2013. Soon after, Schoenbauer was connected with a clinical trial of Tecentriq out of Georgetown University. “Almost immediately, the cough was going away,” his wife, Frances, said. “It worked so fast, I couldn’t believe how good he was feeling.” Schoenbauer, who still gets Tecentriq every three weeks, is active and walks to the mall in his Maryland town every morning. He’s in remission.

Still there are some major caveats. First, not everyone is responding to the drugs — for advanced stages of melanoma, the number of people still alive after two years was about 35%, compared to 29.7% over the same time for those taking chemotherapy. And sometimes new checkpoint inhibitors under development fail key trials.

Source: http://uk.businessinsider.com/

New Immunotherapy Destroys Almost All Types Of Blood Cancer

cancer in bloodExperimental, living T-cell* therapy shows promise for treating advanced disease, making immunotherapy a ‘pillar’ of cancer care. Fred Hutch’s Dr. Stan Riddell and colleagues are making significant strides in this exciting field, and continue to refine ways to use the human immune system to overcome cancer and other diseases.

Twenty-seven out of 29 patients (more than 93%) with an advanced blood cancer who received an experimental, “living immunotherapy as part of a clinical trial experienced sustained remissions, according to preliminary results of the ongoing study at Fred Hutchinson Cancer Research Center.

Some of the patients in the trial, which began in 2013, were originally not expected to survive for more than a few months because their disease had previously relapsed or was resistant to other treatments, said Dr. Stanley Riddell, an immunotherapy researcher and oncologist Fred Hutch. Today, there is no sign of disease.

He shared the results as part of an update on new adoptive T-cell therapy strategies for cancer at the annual meeting of the American Association for the Advancement of Science in Washington, D.C. Riddell, who has studied how to empower the immune system to effectively treat human disease for more than 25 years, said that progress now being made, underscored by these latest results, is finally making immunotherapya pillar of cancer therapy.” But, he cautioned, “Much like chemotherapy and radiotherapy, it’s not going to be a save-all.” Some patients may require other treatments. The trial is designed to test the safety of the latest iteration of an experimental immunotherapy in which a patient’s own T cells are reprogrammed to eliminate his or her cancer. The reprogramming involves genetically engineering the T cells with synthetic molecules called chimeric antigen receptors, or CARs, that enable them to target and destroy tumor cells bearing a particular target. Trial participants include patients with acute lymphoblastic leukemia, non-Hodgkin lymphoma and chronic lymphocytic leukemia.

* T cells are white blood cells that can detect foreign or abnormal cells, including cancerous ones, and initiate a process that targets those abnormal cells for attack. But even when triggered, the natural immune response to a tumor is often neither strong nor persistent enough to overcome cancer cells.

Source: https://www.fredhutch.org/

Injectable 3D Vaccine Fights Cancer and HIV

One of the reasons cancer is so deadly is that it can evade attack from the body’s immune system, which allows tumors to flourish and spread. Scientists can try to induce the immune system, known as immunotherapy, to go into attack mode to fight cancer and to build long lasting immune resistance to cancer cells. Now, researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard’s School of Engineering and Applied Sciences (SEAS) show a non–surgical injection of programmable biomaterial that spontaneously assembles in vivo into a 3D structure could fight and even help prevent cancer and also infectious disease such as HIV. Their findings are reported in Nature Biotechnology.

dentritic cells
A microscope image shows many of the immune system’s dendritic cells that were collected from a 3D scaffold three days after in vivo injection. The 3D scaffold effectively recruits and activates the dendritic cells to trigger an immune response against specific cells, such as cancerous cells

We can create 3D structures using minimally–invasive delivery to enrich and activate a host’s immune cells to target and attack harmful cells in vivo,” said the study’s senior author David Mooney, Ph.D., who is a Wyss Institute Core Faculty member and the Robert P. Pinkas Professor of Bioengineering at Harvard SEAS. “Nano–sized mesoporous silica particles have already been established as useful for manipulating individual cells from the inside, but this is the first time that larger particles, in the micron–sized range, are used to create a 3D in vivo scaffold that can recruit and attract tens of millions of immune cells,” said co-lead author Jaeyun Kim, Ph.D., an Assistant Professor of Chemical Engineering at Sungkyunkwan University (Korea) and a former Wyss Institute Postdoctoral Fellow.
Source: http://wyss.harvard.edu/