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THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTE R AT JOHNS HOPKINS SPECIAL ISSUE BLOOMBERG~KIMMEL INSTITUTE for CANCER IMMUNOTHERAPY “Immune therapy is a game changer. We need more research to take us the rest of the distance, but we don’t think there is a single cancer that the patient’s own immune system ultimately can’t beat .” –Cancer Immunologist Drew Pardoll , M.D., Ph.D. 2016/2017 2 PROMISE & PROGRESS JOHN RYAN IS AMONG THE MANY PATIENTS WHO HAVE BENEFITTED FROM A PROMISING NEW IMMUNE THERAPY CALLED ANTI-PD1. THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 3 The Final Frontier? Immune Therapies Break Through Cancer’s Protective Barriers 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 cance r 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 empower 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 cells. Researchers and clinicians at the and others unleash the commands that like they have cancer. Knowing what Kimmel Cancer Center have worked send the immune cells to work against it. cancer treatment is “supposed” to be together with experts throughout Johns These types of immune therapies have like—many having already experienced Hopkins, using science to follow the had success alone, but perhaps their it—they worry that they feel too well. Man y clues and bring the world what may be greatest power will come in combining ask: “If I feel this healthy, could the treat - a universal treatment for cancer. Cancer them and, through precision medicine, ment really be working?” immunology and melanoma expert using the biological clues within each pa - The answer, experts say, is a resound - Suzanne Topalian calls immunotherapy tient’s cancer to guide treatment. ing “yes,” and the Kimmel Cancer Center “the common denominator.” Leading the way are scientists, like is leading the way with its unprecedent ed Drew Pardoll and Elizabeth Jaffee , findings echoing through the laboratorie s who have been at work for more than 30 and waiting rooms of medical instituti ons, years de ciphering the mechanisms of the community hospitals, and cancer clinics im mune system, how it works and why it all over the world. all too often does not work against can - “This is oncology of the future,” says cer. As students of the immune system, William Nelson , Kimmel Cancer Cente r Pardo ll, Jaffee, and others understood Director, “and the future is now.” that the characteristics of the immune system should make it the perfect anti - A Game Changer cancer weapon, but if the cancer cell was As long as cancer has been a recognized DREW PARDOLL AND ELIZABETH JAFFEE , CIRCA 1989. complex in its molecular construction, disease, doctors have believed the power the intricacies of the immune system to eliminate it existed within the immune were equally complicated. system, but attempt after attempt to Immune-based therapies reflect a dif - Unlike viruses and bacteria that are unlock this potential has largely failed. feren t approach to treatment. Instead of easi ly recognized by our immune system The potential always existed, but the key targeting cancer cells, the new therapies becaus e they are so different, cancer orig - information needed to turn this promise target immune cells in and around cance rs. inates from our own cells. As a result, it into real treatments was locked away Some treatments increase the number of has all of the cellular mechanisms that inside the DNA of tumor and immune immune cells summoned to the tumor, are used by normal cells at its disposal. 4 PROMISE & PROGRESS 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.” Cancer co-opts them selectively, using ability to dodge an immune attack are Immune Checkpoint them like superpowers to grow, spread, being revealed, and the results, though and cloak themselves from the immune admittedly early, are like nothing that has Blockades More than 8000 practicing oncologists system. ever been seen in cancer medicine. Utter and clinical cancer scientists from all It took time for the technology to destruction of the most resistant, lethal over the world filled the lecture hall at catch up with the scientific ideas, but the tumors is occurring across many cancer the 2015 annual meeting of the American invincible cancer cell may have finally types and with few side effects. Patients Society of Clinical Oncology (ASCO). met its match. This Kimmel Cancer who were months, even weeks, from It’s not the first time a standing-room- Center team of multispecialty collabora - dying are alive and well, some five years only crowd has come there to hear a tors—seasoned investigators and young or more after treatment. Kimmel Cancer Center cancer expert clinician-scientists—has figured out ho w It was what Pardoll and Jaffee imag - discuss one of the most promising new to reset the cellular controls hijacked by ined three decades ago when they first cancer therapies in decades—immune the cancer cell and restore power to the began studying the immune system— checkpoint blockade. This time, cancer immune system. In a convergence of perhaps even better. immunology expert Suzanne Topalian wa s immunology, genetic, and epigenetic there as the David A. Karnofsky Memoria l findings, the secrets of the cancer cell’s The secrets of the cancer cell’s ability to dodge an immune attack are being revealed, and the results, though admittedly ear ly, are like nothing that has ever been seen in cancer medicine . THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER at JOHNS HOPKINS 5 “Cancer cells take control of a valuable immune response regulator and turn it on its head. The anti-PD-1 therapy allows us to seize that power back. ” Award and Lecture recipient for “out - types of therapy, oncologists wanted to ongoing after many years,” says Pardoll. standing contributions to the research, know more. Scholarly journals and the These long-lasting responses that contin - diagnosis, and treatment of cancer.” In news media alike were reporting on ued even after therapy was stopped and 2012, Thoracic Oncology Program Direc - drugs that caused lethal melanoma skin caused few side effects are the reason tor Julie Brahmer presented findings on cancers, kidney cancers, and lung can - the auditorium was filled to capacity an immune checkpoint blockade study in cers to melt away and stay away. with doctors anxious to learn how and lung cancer. It marks a changing tide in The therapies are so new—first teste d when they could get this new therapy for clinical cancer research. Immunology in patients in 2006—that the Kimmel their patients. studies had never before received this Cancer Center immunology team readily The source of the excitement is an level of attention at ASCO meetings. admits there is much left to learn. “We immune target called PD-1 and a related With remarkable and lasting results don’t know yet what the ultimate survival partner protein on tumor cells called in about 20 to 40 percent of patients with benefit will be, but for some patients in PD-L1. PD-1 is what immunology experts advanced cancers that resisted all other these first trials, the responses are still call an immune checkpoint. Par doll stops short of calling it an immune system AMONG NORMAL CELLS, PD-1 IS NOT A BAD ACTOR, EXPLAINS BLOOD AND BONE MARROW CANCER EXPERT AND IMMUNOLOG Y master switch, but the results in labora - 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.” tory research and these early clinical trials point to it as one of the strongest influ - encers of an immune response to cancer identified so far. It—and likely some othe r similar proteins—is responsible for can - cer’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 present - ing 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 pa - trolling immune system can recognize abnormal cells that don’t belong. “When immune cells come upon something that shouldn’t be there, they generate an im - mune reaction,” says Anders. This is the BOB ANDERS 6 PROMISE & PROGRESS Lessons from the RICHARD JONES EPHRAIM FUCHS, LEO LUZNIK First Immune Therapy SOME OF THE earliest research at the Kimmel Cancer Center that focused on the immune system was in blood and bone marrow cancers and bone marrow transplantation. Cancers of the blood and bone marrow, such as leukemia, lymphoma, and multiple myeloma, pro - vided a unique perspective of normal immune cells, malignant ones, and the magnitude of the immune system’s power system, usually found in a brother or almost all parents, siblings, and children In most cancers, the goal is to engag e sister.

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