With President Obama's recent State of the Union speech addressing the launch of a national precision medicine initiative to further tackle cancer and other diseases, a leading immunotherapy expert from Rutgers Cancer Institute of New Jersey weighs in on where we stand with precision immunology and personalized medicine and what needs to be accomplished. Howard L. Kaufman, MD, FACS, associate director for clinical science and chief surgical officer at the Cancer Institute of New Jersey shared his thoughts as part of an editorial in the Journal of Clinical Oncology (doi: 10.1200/JCO.2014.59.6023), which was published shortly before the President's address.
Q: The concept of precision – or personalized – medicine has evolved over the past decade. How far have we come?
A: Precision medicine is changing the paradigm for how we approach cancer treatment in the modern era. An improved understanding of which genetic mutations are present in individual cancers and how they drive cancer cells to grow has allowed us to develop more specific – or targeted – therapy for each patient. A major advance has also been the ability to rapidly determine the genetic changes in an individual patient, a process that took years just a decade ago, but may now be completed in days or even hours. We also have new drugs that have been developed at a fast pace which can be used to target the mutations. A similar revolution has taken place in immunology, a field that focuses on how the immune system helps to fight infection and other diseases, including cancer. We have a much better understanding of both how the immune system can mediate tumor regression and also know how cancers outwit the immune system. This latter piece of information has resulted in new therapeutic targets and significant advances over the last three years. Just like we can now determine the unique genetic changes in an individual patient's cancer, we can know the immune profile in patients and select appropriate immunotherapy to help treat specific cancers.
Q: You discuss a recently proposed concept called the 'cancer-immunity cycle' in your editorial. What is this and what does it mean for precision medicine efforts?
A: The cancer-immunity cycle is a process through which cancer cells are identified by the immune system and trigger an effector immune response to kill the tumor cells. As various aspects of the cycle have been investigated, it has become increasingly clear how to promote a beneficial immune response and new targets for intervention have been established. Our understanding has also led to several important clinical features of immunotherapy. Whereas chemotherapy and targeted therapy work directly on cancer cells, and often quite rapidly, immunotherapy may take a long time to work because the effect is not directly on the cancer cell but rather on one or more cells of the immune response. The response can take time to develop and the immune system may need to circulate widely throughout the body to both initiate an immune response and then deal with cancer cells in multiple locations. This is, perhaps, not surprising. For example, immunization against the hepatitis B virus may take at least three vaccinations and even then some patients may not develop immunity. Despite the slow onset, however, immunotherapy has a very important benefit and that is when a response occurs it can be quite durable. Thus, unlike chemotherapy and targeted therapy where resistance to treatment develops, immunotherapy effects appear to be long lasting, and in some cases may result in complete eradication of cancer.
Q: What challenges are faced by clinicians and researchers with respect to immunotherapy?
A: Immunotherapy is a new form of treatment and many physicians and nurses may not be familiar with how it works and how to manage the side effects, which are very different than chemotherapy. As mentioned, the responses may be slow to develop and thus treatment often needs to continue even if the cancer does not appear to be responding initially. Many of the side effects are autoimmune in nature in which the immune system is so active it may attack normal tissues. The signs and symptoms of these side effects need to be recognized and effective treatment strategies to contain them need to be implemented to safely treat patients. Other challenges include access to tumor tissue and also immune cells that may be in the peripheral blood or tumor sites. Just like targeted therapy requires a sample of tumor to determine the genetic changes, immunotherapists need to see the tumor and immune cells to determine which responses are active and which may be inhibited by the cancer.
Additional challenges include the need to rapidly identify the immune defects and match appropriate treatments to the patient. This will require clinical trials and having patients participate in such studies will be critically important to confirm the potential for precision immunology in the clinic. The large amount of data generated requires expertise in bioinformatics and biostatistics, and we have relatively few such experts who also have a thorough understanding of tumor immunology. The potential promise is clear because so many new immunotherapy drugs are now in development. The future will include testing of these drugs alone and in various rational combinations and this will require pharmaceutical companies, biotechnology organizations, cancer centers and academic medical centers to partner together in an effort to ensure that the most promising drugs and combination studies can be rapidly conducted.
Q: What is needed to address these hurdles?
A: There are many ways to address these hurdles. First, we need to promote education about tumor immunology and immunotherapy for all interested stakeholders, including physicians, nurses, scientists, patients, and industry. We also need to develop strategies for collecting tumor and blood samples for biomarkers and diagnostic assays that can be done quickly and cheaply while providing predictive value for selecting appropriate treatment approaches. A better relationship between academia and industry will also hasten the pace of drug development to maximize the potential benefit for patients with cancer.
Q: Where do you see precision medicine and tumor immunotherapy efforts in the next ten years?
A: In the future, we will likely be able to determine a patient's cancer risk earlier and have a profile of his or her immune system. This will allow a tailored treatment regimen with the highest likelihood of providing an improved outcome for patients with cancer. There is already some intriguing data that targeting the cancer cell through precision medicine and the immune system through what I have called “precision immunology” can have synergistic activity against cancer. This is best exemplified by melanoma in which both targeted therapy and immunotherapy seem to have a role. Since 2011, seven new drugs have been approved for the systemic treatment of advanced melanoma, three are targeted therapy and four are immunotherapy agents. Clinical trials combining these drugs are well under way.
Rutgers Cancer Institute of New Jersey