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Promise and Progress - The Final Frontier? Immune Therapies Break Through Cancer’s Protective Barriers

Promise & Progress: Special Issue Bloomberg - Kimmel Institute for Cancer Immunotherapy
Issue No. 2016

The Final Frontier? Immune Therapies Break Through Cancer’s Protective Barriers

Date: March 23, 2016

Immune therapy is recognizably different from all conventional cancer therapies. Imagine a cancer treatment that works without making patients sick or causing their hair to fall out.  Doctors and nurses agree it is unlike anything they have ever witnessed in the world of cancer medicine. Gone are the iconic bald heads that immediately identified a person—inside or outside of the hospital—as a cancer patient.  Like no other disease, cancer has traumatized the human population with its lethality and toxic treatments.  That’s all changing now, as therapies that empowers the body’s own natural defenses are at last becoming a reality and providing unparalleled, long-lasting responses across many cancer types, and even in the most advanced and treatment-resistant cancers.

Patients are saying they don’t feel like they have cancer. Knowing what cancer treatment is “supposed” to be like—many having already experienced it—they worry that they feel too well.  Many ask: “If I feel this healthy, could the treatment really be working?”

The answer, experts say, is a resounding “yes,” and the Kimmel Cancer Center is leading the way with its unprecedented findings echoing through the laboratories and waiting rooms of medical institutions, community hospitals, and cancer clinics all over the world.

“This is oncology of the future,” says William Nelson, Kimmel Cancer Center Director, “and the future is now.” 

A Game Changer

As long as cancer has been a recognized disease, doctors have believed the power to eliminate it existed within the immune system, but attempt after attempt to unlock this potential has largely failed. The potential always existed, but the key information needed to turn this promise into real treatments was locked away inside the DNA of tumor and immune cells. Researchers and clinicians at the Kimmel Cancer Center have worked together with experts throughout Johns Hopkins, using science to follow the clues and bring the world what may be a universal treatment for cancer. Cancer immunology and melanoma expert Suzanne Topalian calls immunotherapy “the common denominator.”

Immune-based therapies reflect a different approach to treatment. Instead of targeting cancer cells, the new therapies target immune cells in and around cancers. Some treatments increase the number of immune cells summoned to the tumor, and others unleash the commands that send the immune cells to work against it.  These types of immune therapies have had success alone, but perhaps their greatest power will come in combining them, and through precision medicine, using the biological clues within each patient’s cancer to guide treatment.

Leading the way are scientists, like Drew Pardoll and Elizabeth Jaffee, who have been at work for more than 30 years deciphering the mechanisms of the immune system, how it works and why it all too often does not work against cancer.  As students of the immune system, Pardoll, Jaffee, and others understood that the characteristics of the immune system should make it the perfect anticancer weapon, but if the cancer cell was complex in its molecular construction, the intricacies of the immune system were equally complicated.

Unlike viruses and bacteria that are easily recognized by our immune system because they are so different, cancer originates from our own cells. As a result, it has all of the cellular mechanisms that are used by normal cells at its disposal. Cancer co-opts them selectively, using them like superpowers to grow, spread, and cloak themselves from the immune system.

It took time for the technology to catch up with the scientific ideas, but the invincible cancer cell may have finally met its match. This Kimmel Cancer Center team of multispecialty collaborators—seasoned investigators and young clinician-scientists—have figured out how to reset the cellular controls hijacked by the cancer cell and restore power to the immune system. In a convergence of immunology, genetic, and epigenetic findings, the secrets of the cancer cell’s ability to dodge an immune attack are being revealed, and the results, though admittedly early, are like nothing that has ever been seen in cancer medicine.  Utter destruction of the most resistant, lethal tumors is occurring across many cancer types and with few side effects. Patients who were months, even weeks, from dying are alive and well, some five years or more after treatment.

It was what Pardoll and Jaffee imagined three decades ago when they first began studying the immune system—perhaps even better.

Immune Checkpoint Blockades

More than 8000 practicing oncologists and clinical cancer scientists from all over the world filled the lecture hall at the 2015 annual meeting of the American Society of Clinical Oncology (ASCO). It’s not the first time a standing-room-only crowd has come there to hear a Kimmel Cancer Center cancer expert discuss one of the most promising new cancer therapies in decades—immune checkpoint blockade. This time, cancer immunology expert Suzanne Topalian was there as the David A. Karnofsky Memorial Award and Lecture recipient for “outstanding contributions to the research, diagnosis, and treatment of cancer.”  In 2012, Thoracic Oncology Program Director Julie Brahmer presented findings on an immune checkpoint blockade study in lung cancer. It marks a changing tide in clinical cancer research. Immunology studies had never before received this level of attention at ASCO meetings.

With remarkable and lasting results in about 20 to 40 percent of patients with advanced cancers that resisted all other types of therapy, oncologists wanted to know more. Scholarly journals and the news media alike were reporting on drugs that caused lethal melanoma skin cancers, kidney cancers, and lung cancers to melt away and stay away.

The therapies are so new—first tested in patients in 2006—that the Kimmel Cancer Center immunology team readily admits there is much left to learn. “We don’t know yet what the ultimate survival benefit will be, but for some patients in these first trials, the responses are still ongoing after many years,” says Pardoll.  These long-lasting responses that continued even after therapy was stopped and caused few side effects are the reason the auditorium was filled to capacity with doctors anxious to learn how and when they could get this new therapy for their patients.

The source of the excitement is an immune target called PD-1 and a related partner protein on tumor cells called PD-L1.  PD-1 is what immunology experts call an immune checkpoint. Pardoll stops short of calling it an immune system master switch, but the results in laboratory research and these early clinical trials point to it as one of the strongest influencers of an immune response to cancer identified so far. It—and likely some other similar proteins—is responsible for cancer’s ability to avert an immune attack.

There are two main actions at play in an immune reaction. The first is a “go” signal.  “Our cells are constantly presenting our own proteins to our own immune system,” explains pathologist Bob Anders. One can think of DNA as the blueprint of a cell, and the proteins its genes encode are its building blocks.  A protein from a mutated gene looks different than its normal counterpart. In the same way it recognizes bacteria and viruses, the patrolling immune system can recognize abnormal cells that don’t belong.  “When immune cells come upon something that shouldn’t be there, they generate an immune reaction,” says Anders.  This is the go signal.  When the job is done and the invading cells are taken care of, the immune system issues a “stop” signal.

These stop signals are controlled by immune checkpoints like PD-1. In cancer, malignant cells hijack the “stop” signal to maintain their own survival. They send a deceptive message to cancer-killing immune cells that there is no problem. Immune cells arrive at the tumor, but they are duped with a false message that everything is OK. “Essentially, they’re told to go home. There is nothing to see here,” says pathologist Janis Taube.

Taube and Anders describe a scenario in which a tumor is spreading, and as immune cells come in to try to remove the cancer, the cancer turns up the volume on PD-1, a signal that turns the immune cells off. “The tumor cells use our own physiology against us,” says Anders.

The “volume” of the PD-1 stop signal is controlled in the cancer cell by the expression of one or both of two partner proteins called PD-L1 and PD-L2.  In solid tumors, like melanoma and lung cancer, PD-L1 has received the most attention today, but PD-L2 appears to play an important role in cancers that start in the blood and lymph nodes, such as leukemia and lymphoma. “We see PD-L1 frequently in melanoma,” says Taube. “PD-L1 is expressed on the surface of the tumor cell. When you see it through the microscope, it looks like someone outlined the cells with a marker.  It forms an armor that protects the cancer cell from the immune system.”

Giving patients a drug, known as an anti-PD-1 checkpoint blocker, for its ability to interrupt PD-1 signaling as well as the communication between PD-1 and PD-L1 and PD-L2, removes the stop signal and re-engages the immune system.

Among normal cells, PD-1 is not a bad actor, explains blood and bone marrow cancer expert and immunology collaborator Jonathan Powell. “It’s actually a good thing. It’s the means by which the immune system regulates itself. It makes sure the immune system doesn’t overdo its job,” he says. It’s the cancer cell that once again assumes the role of villain. PD-1 is an immune mechanism that has been usurped by the cancer cell. “Cancer cells take control of a valuable immune response regulator and turn it on its head,” he says. “Anti-PD-1 therapy allows us to seize that power back.”

Unbelievable Patient Responses

John Ryan is among the many patients who have benefitted from the anti-PD-1 therapy being discussed at ASCO.

Ryan, 71, began experiencing symptoms in 2013 when he coughed up a small amount of blood. The husband and father of eight thought it was strange, but with no pain or other symptoms he was stunned to learn he had the most advanced stage of a common form of lung cancer known as non-small cell lung cancer.  The cancer had already spread to a rib.

There are few diagnoses worse than late stage lung cancer. The cancer kills more people than any other type of cancer, and few patients survive once it has spread. At this stage, the cancer is treatment resistant, responding for a brief time to chemotherapy or cancer-gene-targeted therapies, but almost always resurging even stronger.

Medically speaking, Ryan’s diagnosis was Stage 4 non small cell adenocarcinoma of the lung. “One of my sons was graduating from college, and my daughter was about to leave for a study abroad. I wondered if I would live long enough to see my son graduate or to welcome my daughter back home,” Ryan recalls.

For a time, the chemotherapy worked, but the treatment came at great physical cost, and these side effects were worsening.  The simplest tasks became difficult. His body was weakening, and worse, he learned his cancer was no longer responding.  Genetic testing of his tumor did not reveal any mutations that would make him a candidate for targeted therapies. It seemed he was out of options, until his doctor suggested he go to the Kimmel Cancer Center and meet with lung cancer expert Julie Brahmer.

Brahmer was one of the lead investigators on an experimental clinical study of the anti-PD-1 therapy in a variety of advanced cancers. Ryan’s form of lung cancer was among the cancers that showed unprecedented responses.   

“Before I began treatment, I struggled to sit at my kitchen table.  After just four treatments, the tumor shrunk by 65 percent and I felt like a human being again,” says Ryan. A few more treatments and Ryan’s rapidly growing lung cancer was nearly gone and the cancer that spread to his rib was eliminated.  His only side effect was some minor skin irritations he compared to a mosquito bite.

Ryan is not an isolated case. Topalian and Brahmer say about one-quarter of the lung cancer patients in their studies responded to the treatment. The numbers are even higher for melanoma and kidney cancer patients.

Anti-PD-1 is not the first checkpoint blockade therapy, but it is the first to work beyond melanoma in as many as 14 other cancer types, and that’s the pivotal difference that has excited the cancer world.

The Lung Cancer Difference

The first clinical reports of checkpoint inhibitors in melanoma were exciting and peaked interest, but excitement was tempered because the few successes in immune therapy over the last three decades had also been primarily in melanoma and kidney cancer.  There have been documented cases of these cancers occasionally going into spontaneous remission, so experts long maintained that, by nature, these types of cancers had a way of engaging the immune system. No other type of cancer was considered to be responsive to immune interventions. The new therapy was greeted with guarded optimism.

That all changed in 2012 when the Kimmel Cancer Center group published the results of anti-PD-1 therapy in lung cancer patients. Lung cancer had never before responded to an immune therapy, and the remarkable activity of anti-PD-1 in a small number of lung cancer patients proved what Pardoll and other cancer immunologists long believed—if understood, the immune system could be used to fight any cancer.  “Anti-PD-1 has become a cancer juggernaut,” says Pardoll.

Pardoll first became interested in the protein in 2000 when he came upon PD-1’s second partner, PD-L2. Lieping Chen, a collaborator of Pardoll’s at the Kimmel Cancer Center who is now at Yale, had just discovered PD-L1 and showed that it’s expression in human lung cancer cells was highly elevated compared to normal cells.  Although lung cancers had not responded to other past immune therapy attempts, this discovery provided new evidence that it had the potential to work and was the reason the Kimmel Cancer Center team included lung cancer patients in the first anti-PD-1 trial.

Powell is excited about the success of PD-1 in patients, but he is also enthusiastic about what he sees as a triumph of science. “What we have learned is so encouraging,” he says. “The mere fact that we can block a checkpoint and make a tumor go away is an incredibly important finding because it tells us that the human body—even without help from immunologists—has an immune response to cancer. The problem is that the response is being blocked. That concept, and the fact that it is true in people, is exceedingly important.”

“This is yet more evidence that well-thought-out, consistent and collaborative research pays off,” says William Nelson, the Kimmel Cancer Center Director.  “Anti-PD1 is a triumph of team science.” It is this willingness to follow leads and seek out other experts that can inform the process that continues to position Johns Hopkins as a leader in transitioning laboratory science into pioneering cancer therapies, he says.

“We developed this one from scratch at the Kimmel Cancer Center,” says Pardoll.  As soon as the components of the PD-1 pathway were discovered in 2000, Pardoll, Topalian, Brahmer, and immunology and genitourinary cancer expert Chuck Drake, saw the potential of blocking it. They began working with the small biotech company Medarex to develop the first anti-PD1 antibody in the laboratory and took it to patients. They too found strong responses in melanoma, but it was Brahmer’s lung cancer patients that were game changers.

This was the moment Pardoll and Topalian, who are not only research partners but also husband and wife, were waiting for. It was a belief Pardoll had staked his career on, and one that caused Topalian to change course from a career as surgical oncologist to immunology, working as a National Cancer Institute scientist alongside cancer immunology pioneer Steven Rosenberg for 20 years before coming to the Kimmel Cancer Center.

Rosenberg’s research of interferons and interleukins, cellular messengers critical to immune responses, garnered similar excitement in the 1980s as a potential broad-based immune treatment for cancer. The cover of Time magazine boasted the headline “Interferon: The Cure for Cancer.” When the celebrated treatment failed to live up to expectations—most of which had been generated by an eager news media desperately waiting for the grand-slam victory that had been promised when the “war against cancer” was announced in 1971—the field of cancer immunology was nearly crushed. To be fair, interleukin-2 treatment, while a difficult treatment for patients, continues to be used occasionally today and is highly effective in some patients with melanoma and kidney cancer. However, instead of being the blockbuster immune therapy people had hoped for, it was a start. “It was the first evidence that a drug that acted only through the immune system could fight very advanced cancer,” says Topalian. “That was important because it told us we were on the right track with immunotherapy and needed to keep working on this.”

In fact, many outside the field of cancer immunology had begun to doubt the promise of immune treatments in cancer. Immunotherapy discussions at the large national cancer meetings were sparsely attended, and research funding was hard to come by. The Kimmel Cancer Center immunology team remained undeterred. They knew the power of the immune system and their convictions were cemented in this truth. The challenge was channeling this power into real therapies.

The promise of immune therapy is changing the way new therapies are studied and evaluated. Chemotherapy poisons cells dividing quickly, including immune cells. This toxic effect is the cause of the common side effects like hair loss, nausea, and infection risk due to a compromised immune system.  Immune therapies appear to work more slowly over time, and it’s looking now like they work better for longer.  Some of this was learned almost serendipitously as cancers that initially looked like they were not responding to immune treatments, with more time began to shrink with more time.  “The immune system has been living with cancer for years. To make it not be so happy living with the cancer takes some time,” says Drake.

Eventually, it all rested upon what was learned with science and technology—powerful new ways to look inside the DNA of cancer cells and computerized data mining that measures and quantifies the subtlest of changes and differences among seemingly similar cancers.

The mechanisms that make therapy work in one patient and not in another are now being teased out.  Treatments that worked only in a small subset of patients were once deemed failures. Now, in an era of precision medicine that uses molecular markers to identify the right treatment for each patient, the options are much broader and the outlook is significantly brighter.

First There Were Cancer Vaccines

Cancer vaccines were one of the first immune treatments studied by Kimmel Cancer Center investigators. Early research on cancer vaccines by immunologist and pancreatic cancer expert Elizabeth Jaffee proved the ability to successfully recruit immune cells to tumors, and even had some therapeutic benefit.  All too often, however, the immune cells—called to the tumor by the vaccine in large numbers—did not fully attack the cancer.

Vaccines can peak the immune response in days, calling immune cells to the tumor site. To reverse tolerance of the cancer—characterized by immune cells flooding to the tumor site but not taking action—can take time. It may also require additional kinds of immune therapies. Some patients’ immune systems are on the edge, requiring just a vaccine to make them respond. Others need more.

Jaffee and Daniel Laheru, co-directors of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care, are leading the way in cancer vaccine therapy, and their target is one of the deadliest of cancers.

Jaffee began working on a pancreatic cancer vaccine more than two decades ago. To make vaccine therapy a reality, she became an expert in FDA regulations and vaccine manufacturing, and she opened a GMP (good manufacturing practices) facility at the Kimmel Cancer Center to make vaccines for clinical studies.

Jaffee, Laheru, and young investigators Dung Le, Lei Zheng, Erik Lutz and others are testing various versions of the vaccine, built from pancreatic cancer cells that have been rendered dormant with radiation and engineered to recruit immune cells to track and attack malignant cells anywhere in the body and to continue to do it indefinitely.

In some patients, the original iteration of the vaccine has worked remarkably. Patients like nearly 20-year survivor Kathleen Dowell, 12-year survivor Donna Bender, and eight-year survivor Nancy Amato were given months to live when their pancreatic cancers persisted after surgery, chemotherapy, and radiation therapy. Jaffee’s vaccine continues to keep their cancers in check.

Because it is perhaps one of the only treatments that make any real difference in long-term survival for this most aggressive of cancers, the vaccine has attracted worldwide attention. Clinic coordinator and research nurse Barbara Biedrzycki receives more than 60 calls per month from patients who want to get the vaccine. Once after an appearance by Jaffee on The Dr. Oz Show, the clinic was flooded with more than 1,000 inquiries from patients all over the country. “There is no other cancer center doing this kind of work,” say Zheng.

With funding from the Skip Viragh Foundation, Laheru, Zheng, Lutz, and Le are working with Jaffee to optimize the effects of her pioneering vaccine. They are making tweaks in timing of vaccination and changes to its composition and delivery that they hope will boost its cancer-killing capabilities and make the vaccine a treatment option for many more patients.

One of their new approaches is to give the vaccine before surgery. “Pancreatic cancer is notorious for being in areas outside of the pancreas, and the vaccine allows us to get ahead of the disease and get microscopic cancer cells that surgery might miss,” says Laheru.

Other variations include combined treatments.  In some patients, giving the immune-modulating drug cyclophosphamide before the vaccine causes immune structures to form inside tumors that help regulate immune cell activation. “These organized immune structures do not naturally appear in pancreatic cancers,” says Zheng. “This suggests that there has been significant reprogramming of immune cells within the tumor.”  There is evidence that adding a checkpoint blockade like anti-PD-1 treatment to the mix could further enhance immune activity.

Another combined approach adds a second kind of vaccine, a weakened version of the bacterium listeria. The listeria is genetically modified to be safe for humans but stimulates an immune response against the protein mesothelin. Ralph Hruban, pathologist and Director of the Sol Goldman Pancreatic Cancer Research, found mesothelin in high levels on the surface of pancreatic cancer cells, and Jaffee and Le believe the protein helps pancreatic cancer cells to grow and spread.  “The combination essentially trains the body to recognize and attack pancreatic tumors,” says Le.

Ongoing research has revealed that mesothelin is over-expressed in many cancers, including about one-half of lung cancers, mesotheliomas, ovarian cancers, and stomach cancers. As a result, the vaccine is now being tested in lung cancer and mesothelioma, and Kimmel Cancer Center immunology expert Leisha Emens will lead a trial testing it in ovarian cancer.

Patient Perspective

Sarasota internist Jonathan Greco, 58, is among 90 patients enrolled in a clinical trial to test the effectiveness of a cyclophosphamide, GVAX, listeria, and anti-PD-1 quadruple combination.

After nine weeks of chemotherapy at a cancer clinic near his home, Greco says he felt worse than he ever had his life. He told himself it was worth it because, as bad as he felt, his doctors told him it was causing his pancreatic cancer to shrink enough that it could be cut out with surgery.

As a physician, Greco knew of Johns Hopkins expertise in the Whipple procedure, the primary surgical treatment for pancreatic cancer.  Johns Hopkins surgeons perfected the procedure, perform more of them, and train more new surgeons how do the procedure than any other institution in the world. With this in mind, Greco scheduled a consultation at the Kimmel Cancer Center’s Skip Viragh Center.

At his consultation, he learned the chemotherapy hadn’t worked. In fact, his cancer was quite advanced, and a Whipple procedure would not help him. “I’m so thankful I came to Johns Hopkins,” says Greco. “If I had listened to the doctors in Florida and went ahead with the surgery, I’m certain I would have died.”

Greco continued to do his research. He was familiar with immune therapy and went to the National Cancer Institute’s website to search for experimental treatments and information. “Johns Hopkins clearly had the most immunotherapy experience. It was evident they had been doing this longer than anybody,” says Greco.

He enrolled in a clinical trial designed and led by Elizabeth Jaffee and Dung Le that is the centerpiece of a Stand Up To Cancer pancreatic cancer dream team directed by Jaffee.  It combines treatments with the vaccine-enhancing drug cyclophosphamide, the immune-activating GVAX vaccine, mesothelin-targeting listeria, and the immune checkpoint blockade with anti-PD-1. The pancreatic cancer GVAX vaccine was developed by Jaffee with Viragh funding and is manufactured at a GMP facility in the Kimmel Cancer Center that she opened and directs.

The combined therapy represents a culmination of immunology laboratory and clinical science, joining the strength of several immune-targeted therapies in an attempt to topple one of the most lethal cancers. Jaffee and Le hope the combination will pack the immune punch needed to break the resistance of pancreatic cancer.

“I feel fortunate to be one of the 90 patients participating in this trial,” says Greco. Le says it’s too early in his treatment to measure the effect the treatment is having on his cancer or to know what the long-term impact will be.  After his experience with chemotherapy, Greco says he is grateful for a treatment that doesn’t make him sick. “I feel like myself again. I feel great. I swim everyday, and I’m still seeing patients. I feel like I’m cured.”

Jonathan Greco is currently in the GVAX phase of his treatment, and at this appointment nurse Angela Van Tassel administers the second of nine vaccinations to pancreatic cancer patient Jonathan Greco. Greco receives six total injections per vaccination—two in each arm, and one in each thigh. The vaccine is administered just under the skin, with each injection taking about a minute. “It feels like a bee sting,” he says. “In a couple of days, it will start to itch.”  The itching is an immune reaction, says Van Tassel. 

Then Came PD-1

The first patients were treated with anti-PD-1 in 2006 as part of a small clinical trial led by Brahmer and funded by Medarex, now part of pharmaceutical giant Bristol- Myers Squibb. The scientific studies to better understand how anti-PD-1 was working were supported by the Melanoma Research Alliance, the National Cancer Institute, and faculty support Topalian received from the Kimmel Cancer Center and the Department of Surgery when she came to Johns Hopkins.

Fast forward to 2015, and people were getting very excited again about immunotherapy when the attention of the cancer world—some 30,000 people attending the ASCO meeting—was fixed on the findings from the Kimmel Cancer Center cancer immunology team as Topalian explained this immune checkpoint that could be reset with a drug.  In addition to igniting an immune response against cancer, the anti-PD-1 drug could be given in the outpatient clinic and caused very few side effects. The media, including Science, one of the world’s leading scientific journals, dubbed it a breakthrough. “The attention it was receiving and the number of people who wanted to learn about our work were signs that immune therapy was now part of mainstream oncology,” says Topalian.

Topalian, who has been there through many of the ups and downs in cancer immunology, prefers to call it an evolution. To the public and even scientists outside of cancer immunology, it may seem like an overnight sensation. In reality, it was the product of research that occurred over decades with many contributors, when all but the immunology diehards weren’t looking. “It’s been a long process,” she says. “Today, it’s celebrated, but over the last 30 years there have been many things that looked great in the laboratory that did not translate into patients.” Although cancer immunology experts had held steadfast to their convictions that they could figure out a way to make the immune system work against cancer, outside of the field there were whispers of defeat.  “In 2012, with our publication in the New England Journal of Medicine on a 300-patient clinical trial of anti-PD-1, everything came together. It was our moment,” she says.

A Milestone in Cancer Medicine

Remarkable responses were occurring in a significant number of patients, putting the framework for a potentially broad-based treatment for cancer in place. This glimmer quickly ignited into a spark and continues to gain momentum as collaborations across many specialties at Johns Hopkins are expanding its benefit to other cancers.

This success revealed that the immune system could be employed against cancers beyond melanoma and kidney cancer. As important, it provided definitive proof that there was a common force at work to shut down an immune response to cancer.

The most recent clinical study provides clear evidence that for lung cancer patients whose immune cells express PD-1 or whose tumor cells express PD-L1, immune therapy works better than the best chemotherapy drugs and with far fewer side effects.  In addition, patients with late-stage lung cancers frequently become resistant to chemotherapy, but Brahmer says that patients who respond to immune therapy tend to continue responding. “In my 20 years in practice, I have never seen anything like this. We’re reporting three-year and more survival rates in lung cancer patients who honestly would not typically be around,” says Brahmer.  “This is truly a milestone in cancer medicine.”

As for how long patients will continue to respond off treatment and whether there are any long-term effects of this type of immune therapy, it’s too soon to know. Pardoll, Topalian and collaborators are working to answer these questions. They also want to make sense of the varied respon