President's Message - July 2018

Dear Colleagues,

Let me begin by congratulating everyone who contributed to the exciting achievement of the Journal for ImmunoTherapy of Cancer (JITC), the Society for Immunotherapy of Cancer's (SITC) open access, peer-reviewed online journal, on its first impact factor of 8.374!

As many of you know, an impact factor – a calculation of the number of citations a publication's articles received in a year by the total number of articles published – quickly communicates to prospective authors the reach and quality of research a publication possesses. The JITC impact factor is the next big step toward an even brighter future for our society's online publication.

Much of the credit goes to JITC Editor-in-Chief Pedro J. Romero, MD, and the many SITC member experts who serve as section editors and reviewers on the journals' Editorial Board. However, JITC would not be what it is today – or further, what it is becoming – without the contributions from the many authors who have submitted their field-changing research to JITC.

Now, five years after our society's launch of JITC, this achievement provides significant validation to the journal as a premier destination for cancer immunotherapy research. I encourage all prospective authors in our field to submit to JITC when considering a venue for your work.

Among the most valuable of JITC's publications are the consensus statements submitted as part of the SITC Cancer Immunotherapy Guidelines. These immunotherapy treatment recommendations play a critical role in educating oncologists and other members of the patient care team on current standards involving U.S. Food and Drug Administration-approved cancer immunotherapy treatments for a growing list of disease states. SITC expanded its Cancer Immunotherapy Guidelines offerings in May when it updated its recommendations on cutaneous melanoma. A manuscript on non-small cell lung cancer is slated to publish in JITC next month.

We're also disseminating these guidelines broadly to increase access. This includes a new, interactive series of SITC Cancer Immunotherapy Guidelines Webinars. These live events will take place approximately two months after manuscript publication and will allow authors to go further in-depth about the treatment recommendations, answer questions and discuss any late-breaking advances in the field since publication.

The first SITC Cancer Immunotherapy Guidelines Webinar will take place Monday, July 30, 6–7 p.m. EDT, focusing on the recent update of the guidelines for cutaneous melanoma. Click here to register for this free opportunity.

The need for ongoing education for clinicians about the latest advancements in immunotherapy for cancer has never been greater. At the American Society of Clinical Oncology's (ASCO) 2018 Annual Meeting, SITC staff fielded numerous questions from attendees, and served as a resource to many visitors of our society's booth at ASCO 2018. If you would like to review highlights of the meeting, SITC published daily scientific reports from the ASCO Annual Meeting, log in to your SITC CONNECT account to access our staffreports from each day of the meeting.

In closing, as you enjoy a little lull in your scientific activities over the summer, and write up the results of your recent studies, I hope you will send those data to JITC, where the new 8.374 impact factor will assure great exposure to your colleagues.

Sincerely,

Lisa H. Butterfield, PhD

SITC President

Staying Alive: My IO Journey

by Jacqueline Smith

On Nov. 29, 2006, during the first semester of my graduate school program, I learned the disease I thought I had beat three years prior had, again, reared its ugly head. I was devastated. The lump I had detected in my bikini line almost a year-and-a-half earlier was not the inflamed lymph node that my gynecologist assured me it was, and it was not the result of some minor infection that my primary care provider’s assistant diagnosed. It was a lymph node filled with cancer.

Upon my diagnosis three years earlier, I was advised by my then oncologist to “watch and wait” because the treatments at that time were highly toxic causing debilitating and irreparable long-term damage. However, this time, watch and wait was not an option.

Jacqueline Smith

I returned to my parent’s home in Orlando, Fla. I visited a number of doctors and specialists. On Dec. 21, 2006, I was told it would be a miracle if I survived another five years. Needless to say, I spent the holiday season drowning in self-pity and worry mixed with anger and resentment.

Though none of us know when we will reach the end, most live everyday with the promise and hope for a new day. However, receiving a cancer diagnosis quickly forces one to face their mortality.

Fortunately, with the New Year came new resolve. I was not going to abandon my dreams. I was not going to let this disease consume every aspect of my life. I decided to fight. I began to research every aspect of melanoma: the disease, surgeries, treatments, treatment centers and specialists.

Every doctor whom I contacted recommended I seek treatment at the H. Lee Moffitt Cancer Center in Tampa, Fla. It was there I was given hope. My surgical oncologist stated that while he could not determine my life expectancy, if I did not have the cancerous lymph nodes removed, there was a high possibility that cancer (melanoma) would kill me. He also expressed hope that I would qualify for a clinical trial.

On March 29, 2007, I had a total right groin lymphadenectomy. It was then that Dr. Vernon Sondak alerted me to a newly opened clinical trial. It was then that I learned what immunotherapy was and decided to rest my fate in its hands.

I became one of the first enrollees in the PEG-Intron trial. For the first three months, I had to go to Moffitt daily, for blood draws. I learned to mix and self-administer the Pegylated interferon. I was encouraged to learn this treatment was less harsh than chemotherapy. I was thankful that I would be able to an outpatient during my care.

Most importantly, I no longer thought about my mortality, but rather focused on my treatment and the potential for being cured.

I endured surgery, PEG-Intron therapy and four months of radiation.

Today, 10 years later, I am thankful to say I am cancer free. As my 10-year, cancer-free survival is due, in part, to the success of an immunotherapy clinical trial, I have decided to dedicate my life to working toward establishing immunotherapy as a standard of care for all cancer patients.

I am now the Policy and Advocacy Manager for the Society for Immunotherapy of Cancer (SITC). At SITC, I am one of many people who work tirelessly to advance the field of immunotherapy in hopes of helping more cancer patients enjoy a better quality of life and transition from long-term cancer free survival to being cured.

Cancer Immunotherapy: Simplified…

by Kushal Prajapati

In the field of cancer research, Cancer Immunotherapy, Immuno-Oncology or I-O have been buzzwords for quite a few years now. For those who are not life science professionals but actively follow the developments in the field, these may be some popular terms come across on TV, newspapers or magazines. Yet for many, including some scientists not very familiar with immunology, the understanding of how immunotherapy could treat cancer remains either elusive or a mystery. In this blog, I will try to simplify some key principles of Immuno-Oncology for anyone who has always wanted to learn more about this revolutionary field.

Our body is nature’s highly sophisticated creation equipped with a very efficient defense called the immune system. This immune system is made up of different kinds of cells, each specialized in carrying out certain tasks. One of the cell types, known as killer T cells, can identify the foreign cells/invaders in the body and kill them (yes, literally). You could think of them as the ‘soldiers’ of your body who know how to find intruders and neutralize them. In Immuno-Oncology, scientists use these T cells to recognize and kill cancer cells. But wait…cancer cells are your own cells, not foreigners, right? Why would T cells kill your own cells?! The answer to this lies in the fundamentals of how the T cells identify their targets.

Every healthy cell in our body needs to present a normal pattern of immunological signals, called ‘antigens’, to be accepted as ‘self’ or ‘body’s own’ by the immune system. However, when a cell incurs numerous genetic mutations and/or the biological processes within it go haywire, this pattern of antigen presentation is changed enough to label the cell as ‘foreign’ in the eyes of the immune system. This is often the case for cancer cells. T cells would then identify the abnormal antigens on cancer cells using their receptor- called T cell receptor - and get rid of these cells. But if it was this simple, then no one would ever get cancer as the T cells would keep killing the cancer cells as and when they arise. Hence, there is something that’s certainly not very efficient about this process. While we don’t completely understand the underlying reasons yet, the scientists have been able to turn the tables on cancer by strengthening the T cells’ anti-tumor activity in two major ways in the clinic so far.

The first one is chimeric antigen receptor (CAR) T cell therapy which enables T cells to recognize the cancer cells that are otherwise undetectable. As we talked about antigen presentation in previous paragraph, it is worth knowing that many cancer antigens exist in forms that are not recognizable by the T cell receptors. Consequently, these antigens always go undetected by the T cells. CAR was designed to overcome this limitation. It combines a part of the natural T cell receptor with a part of an antibody that can recognize a desired antigen (the one that’s unrecognizable by T cell receptor). Just like giving a new tool to a solider to spot a hidden enemy! With this technology, scientists can identify new cancer antigens invisible to the immune system, design CARs against them, and put them into our T cells to empower them to accurately kill those cancer cells.

The second approach, called the ‘check-point’ blockade, basically stops the T cells from being stopped by cancer cells. In general, T cells in our body are always on the call of duty, looking out for threats and dealing with them. In this scenario, our body has natural mechanisms in place to control the T cells from over-reacting and potentially hurting the healthy cells. One such mechanism is ‘check-point’ signaling, wherein the T cells that are over-worked show significant presence of check-point receptors like PD-1 and CTLA-4 which serve as ‘brakes’ on them. It’s when these receptors (brakes) are ‘engaged’ by the molecules called check-point ligands, the T cells slow-down their function or stop completely. This very mechanism is exploited by cancer cells to escape the immune system. They increase the engagement of the brakes (PD1, CTLA-4) on T cells by simply increasing the amounts of check-point ligands- resulting in attenuation of T cell function. To tackle this problem, researchers developed antibodies which block the interaction between check-point receptors and their ligands. This allows the T cells to continue killing cancer cells without stopping! So far, the check-point blockades of PD-1 and CTLA-4 signaling have shown resounding success in treating many cancers in the clinic.

So, do we finally have the magic bullet against cancer? Not quite yet. The clinical success of immunotherapy has been exciting; however, studies show that most patients do not respond to it if they have more aggressive, solid tumors. However, the good news is that years of research work has revealed to us biological reasons (e.g. various ways the cancer fights back against immune system) behind failure of immunotherapies in such cases. As the new treatments developed based on this knowledge make their way into the clinical trials, exciting times are waiting ahead for cancer immunotherapy! 

[Disclosure: This blog is intended to educate general public and non-experts about the basic concepts of cancer immunology and clinically available immunotherapies. The author does not intend to undermine the efforts behind other cancer immunotherapy approaches that are currently under clinical investigation]

Q&A with SITC Vice Presidential Candidate Patrick Hwu, MD

In celebration of Cancer Immunotherapy Month™, we’ve asked SITC leaders to participate in a Q&A series for The Sentinel. We’ve asked them to briefly share why they entered the field, advice they’d share with early career scientists considering a career in cancer immunotherapy and more.

Please see below the Q&A from Patrick Hwu, MD, of University of Texas MD Anderson Cancer Center. Dr. Hwu is a 2018 candidate for SITC Vice President. Learn more about his candidacy here. Voting for the 2018 SITC Election takes place June 14–28, 2018.

1. What initially excited or intrigued you about the cancer immunotherapy field to choose this as your career focus?

When we get a viral infection, we can get very sick, but almost always fully recover. This powerful ability of the immune system to naturally cure viral illnesses has always intrigued me and encouraged me that applying this system against cancer could be impactful. In addition, the non-specificity and toxicity of current cancer therapies, such as chemotherapies, have always seemed unpalatable to me.  T-cells have the ability to distinguish normal peptides from mutated cancer-associated peptides that differ in merely one amino acid. This ability can enable anti-cancer therapies that have high efficacy and low toxicity. Even though immunotherapies in the early days were quite toxic, recent advances have allowed us to get closer to this dream of efficacious therapies without much toxicity. I routinely now have patients who travel to Europe and other distant places on vacation in between their outpatient treatments of immunotherapy. 

2. What advice would you share to an early career scientist contemplating a career in cancer immunotherapy?

Go for it!!  This is an exciting field.  I somewhat envy young investigators entering the field now. We know so much more than we knew when I was starting out, such as many of the immunoregulatory mechanisms of the body, and now have such great techniques like CyTOF and single cell RNA-seq to rapidly answer questions. Be curious, focused, and resilient. Many young investigators are intimidated by challenges with obtaining research funding. But there are in fact many more sources of funding now than traditionally in academia in years past. There is so much potential for us to make a great impact in cancer care, and we need as many talented young minds working on this as possible. Finally, don’t let anyone tell you something is impossible. In the early days, there were only a few of us who believed in immunotherapy and it is gratifying to see how many “converts” we have now.

3. What are three of the biggest hurdles facing researchers in the field, and how do you think they can be solved?

1. Moving immunotherapy responses beyond the common “immunogenic” tumor types.  In my opinion, this is largely due to the lack of sufficient CD8+ T-cells recognizing these cancers, i.e., lack of T-cell priming. This can potentially be solved using cancer vaccines, T-cell therapy and intratumoral immunomodulation, which are all very exciting and promising approaches.
2. Insufficient numbers of young investigators entering the field. Because of the challenges of funding, as well as the lack of enthusiasm for immunotherapy for many years in the past, there is a large deficit of talented, trained immunotherapy investigators. While this is starting to correct itself naturally, we need to move forward with urgency to train additional basic, translational and clinical investigators so we can fulfill the promise of immunotherapy to help the many cancer patients in need of better treatments.
3. Scalability with current approaches. Many of the most exciting current approaches towards immunotherapy, such as T-cell therapy and personalized vaccines, may have challenges with scaling treatments to the population in need in an affordable fashion.  There are many financial pressures on our current health care system, and biologists, engineers, politicians, and the business community must work together to bring these exciting therapies to the many people who need them.

4. What area of research has you most excited for the future of the field, and why?

I am most excited about the many ways we can prime the immune system to induce larger numbers of T-cells able to recognize cancers, many of which are considered “non-immunogenic.” While much of the field has focused on the release of immune checkpoint blockade, this will be ineffective if there is insufficient numbers of specific T-cells recognizing the cancer to begin with. Cancer vaccines, T-cell therapy, and intratumoral immunomodulation (for example, with TLR or STING agonists) are all very exciting areas with much promise. Combining these approaches in a rational way with other immunotherapies and targeted therapies also has much potential.  

Q&A with SITC Vice Presidential Candidate Sandra Demaria, MD

In celebration of Cancer Immunotherapy Month™, we’ve asked SITC leaders to participate in a Q&A series for The Sentinel. We’ve asked them to briefly share why they entered the field, advice they’d share with early career scientists considering a career in cancer immunotherapy and more.

Please see below the Q&A from Sandra Demaria, MD, of Weill Cornell Medical College. Dr. Demaria is a 2018 candidate for SITC Vice President. Learn more about her candidacy here. Voting for the 2018 SITC Election takes place June 14–28, 2018.

1. What initially excited or intrigued you about the cancer immunotherapy field to choose this as your career focus?

I have been fascinated by the immune system since the beginning of medical school when I started volunteering in a research lab working on immunology. Several years later, during my residency in pathology, I matured the decision to devote my research career to study how the immune system interacts with cancer, and how cancer treatment can alter that interaction. Basic immunology had progressed tremendously and after attending a tumor immunology meeting I became really enthusiastic about the possibilities to make progress in cancer treatment. My enthusiasm was further boosted when Jim Allison came to give a lecture and spoke about blocking CTLA-4. It was somewhere in early 2001, before antibodies against CTLA-4 were tested in the clinic, but his vision about the role CTLA-4 blockade in cancer treatment, and how it could be combined with other treatments contributed to shape the direction of my own work.

2. What advice would you share to an early career scientist contemplating a career in cancer immunotherapy?

There is a lot of enthusiasm for the things that work, but you should not be afraid to venture into an area of research that is met with skepticism. Tumor immunology was met with skepticism for a long time. The pioneers who believed in it did not abandon it to work on a more mainstream topic. On the contrary, they worked harder and generated the knowledge that made possible the current revolution in cancer care, with cancer immunotherapy becoming a new treatment strategy that has already saved many lives. There are many critical questions that need to be answered to enhance the effectiveness of cancer immunotherapy. So, think outside the box, do good science, believe in your data, and remember that the value of your work is not really measured by the impact factor of the journals you publish in, but by the impact that it will have on fostering real progress in the field. 

3. What are three of the biggest hurdles facing researchers in the field, and how do you think they can be solved?

Progress can be made only if there is substantial and continuous investment in science at multiple levels (basic, translational and clinical). Scientists and clinicians need to work with patient advocacy groups and other stake holders to leverage public support. Professional societies like SITC are instrumental in leading such efforts. 

Addressing the complexity of tumor-host interactions and understanding how to overcome resistance to immunotherapy requires a multi-disciplinary approach, and a team effort. The current academic structure is still largely based on older paradigms, and is at risk of losing talent that is essential for the research. New types of positions and reward systems that recognize the value of team contributions will help make faster progress and retain the best minds in research.

The bar for success is higher for upcoming and future immunotherapy agents. With increased life expectancy chronic toxicities of immunotherapy may become more important and less acceptable to patients. Improved model systems need to be developed to predict and study the mechanisms of toxicity. 

4. What area of research has you most excited for the future of the field, and why?

I believe that there is a huge potential in leveraging the effects of combination therapies that target different compartments to achieve a synergy with immunotherapy, if done in the context of a system biology approach. I work with radiotherapy, which has the advantage of being a broadly applicable and widely available treatment. But we need to understand how to tailor radiotherapy (and in fact any treatment) the right way for each individual patient. I like to think that there is a combination of specific interventions that will unlock the power of the immune system to reject cancer in every patient, it is just waiting to be discovered!