Dr. Larry Kwak, VP of Translational Research & Developmental Therapeutics

Dr. Kwak, you are a world-renowned physician and cancer research scientist. What was the reason for attending medical school? What motivated you to become a physician?

I give a lot of credit to my family background. I have a wonderful Korean heritage of service to mankind. My maternal grandfather, Oh Chung Soo, was the first Korean to graduate from Massachusetts Institute of Technology (MIT) in 1927, and he later returned to Korea to serve in the government as Minister of Commerce. My parents were both educators. My father, Kwak No Whan, came to the U.S.A. to earn his Ph.D. degree in Physics, and my mother, Oh Chang Sook, came to the U.S.A. for undergraduate college on a piano performance scholarship. As a child, my parents encouraged me to pursue a profession in which I could enhance the welfare of mankind and also instilled in me the values of hard work and motivation.

Dr. Kwak with his laboratory scientists and postdoctoral fellows at City of Hope

I became interested in medical research at a very young age. Actually, it was a pivotal experience during a summer high school internship. I was given a job doing some menial tasks in a hospital clinical laboratory. But my mentor, a pathologist, would invite me into his office every day after work and show me slides under the microscope of cancer cells. Interspersed with those cancer cells were normal immune cells and he would challenge me to think about why those cells – the normal immune cells – were there and if they could one day be harnessed to fight cancer. That exposure sparked my interest in cancer research. From that point on, my education and training were aimed towards that ultimate goal of being able to make discoveries in the laboratory as a scientist and then as a physician to be able to walk over to the clinic and offer those cutting edge treatments to patients.

"Being able to make discoveries in the laboratory as a scientist and then as a physician to offer those cutting edge treatments to patients."

During more than 20 years of commitment in oncology research, you may have gone through various obstacles; can you share some of the most difficult moments in your career?

My first job was at age thirty-four after I finished my M.D. and Ph.D. degrees and clinical residency and subspecialty oncology fellowship at Stanford. I was offered a position to lead my own research program at the National Cancer Institute. It was a wonderful decade at the National Cancer Institute– that’s where some of the earliest discoveries were made by my laboratory in developing one of the first cancer vaccines. We optimized it in laboratory animals and then ultimately were able to take it to patients through the different phases of clinical trials, starting with phase 1 and eventually to phase 3 clinical trial, the last phase in clinical development for a drug, which was ultimately positive.

But it was during the early ground breaking pivotal work 20 years ago that we encountered obstacles to the idea of harnessing the immune system. When we first tested cancer vaccines in the traditional phase 1 clinical trial model; i.e., in patients with advanced cancer burdens, they failed to show any real effectiveness, and this generated many naysayers in the oncology community. But we went back to the drawing board, and testing in mice, we observed that the most effective setting for vaccines was against a minimal cancer burden. In other words, when we combined chemotherapy first, to shrink 90% of the cancer, then gave the vaccine to mop up the remaining microscopic cancer cells, most of the mice were cured. When this principle of combining chemotherapy with the vaccine was then applied to lymphoma patients, the length of their remissions was doubled on average, compared with chemotherapy alone, with some patients staying in remission for 15 years after receiving the vaccine.

So, to me, this is the true meaning of the Ho-Am Prize in Medicine - perseverance. My wife and I traveled to Seoul at the end of May last year to accept the award. And with several Nobel laureates in the audience, it was this message of faith and persistence that I shared to describe my journey in my acceptance speech.

Dr. Kwak delivering Ho-Am prize acceptance speech in Seoul, South Korea

We see that you have been named as one of Time Magazine’s 100 Most Influential People in 2010 along with former President Barack Obama and Steve Jobs, to name a few. This list includes people who are recognized for affecting the world. Can you share with our readers some of the major achievements and outcomes you have accomplished during your professional life?

First, I need to tell you a funny story: I remember receiving an email from the Time Corporation and I didn’t open it right away, because I get a lot of emails and I thought it was a form of spam. And frankly I’d never heard of the Time 100, but I did end up opening it a few days later and I ran it by our communications department. They said “Oh my goodness, this is a major thing and you should definitely go accept it.” So my wife and I both attended the ceremony in New York City - there were so many famous people there (including three other persons of Korean heritage, including Yuna Kim). They actually roll out a red carpet there at the Lincoln Center. Adam Sandler was in line in front of us and the paparazzi were all there snapping his photo; the cameras were going off all the time. And then it was our turn. Our host said, “This is Dr. Larry Kwak” and everything stopped and you could hear everybody whispering, “Who’s that, who’s that?” And then a few seconds later all the cameras just started going off again- it turns out that it didn’t matter who it was after all!

I was honored for my 20 year-long commitment to the science of cancer vaccines. I was fortunate to be recognized, as I think a major component of any recognition is the right timing. I’ve been working in this field of cancer immunotherapy for most of my life, and just now we’re starting to see the fruits of these labors. Specifically, we now have treatments which are actually approved by the FDA in this field and it has opened up a whole new area of cancer research (known as Immuno-Oncology) which is very promising. So I was fortunate that the committee recognized some of my early work as seminal. I was involved in the beginning and was one of the scientists whose research set the groundwork for the successes that we’re seeing today in the clinic.

Dr. Kwak, you are the Vice President and Associate Director for Translational Research and Developmental Therapeutics at City of Hope. What are your key roles, responsibilities, and principles of leading in one of the most comprehensive cancer centers? Also what are the long-term goals and visions that you hope to see the City of Hope to achieve?

As Vice-President and Associate Director for Translational Research and Developmental Therapeutics, my primary responsibility is to shape the next generation of research and treatments for cancer, in general, and lymphoma and hematologic malignancies, in particular, at City of Hope. In my combined roles as a physician, scientist, and mentor, my vision is to assemble and lead research teams to integrate and accelerate basic discoveries from laboratories to clinical development and firstin-human clinical trials of novel “homegrown” therapeutics, such as next generation cancer immunotherapies. I play a key role in the future direction of City of Hope’s precision medicine and teamwork science initiatives.

We see that you are an eminent opinion leader in translational cancer researches. Translational research is a relatively new research discipline which applies findings from basic and fundamental sciences into medical practices. What do you think is the current status, trends, and challenges in translational research? Also, what do you forecast the major changes would be in translational research in the next five years?

The photo of Dr. Kwak and his family

I’m glad you asked, because translational research is what really energizes me. I like to point out that I’ve actually been engaging in this discipline long before the term was coined and before it became popular. True translational research is the idea of taking discoveries from the laboratory and applying them directly to patients. Having training and expertise as a scientist and the perspective and compassion of a physician is one path to such a career, but it’s not the only way. My passion is to inspire the next generation of young physician-scientists with the same vision to see their own research applied in their lifetime, as well as patients to have faith and courage.

My own professional path has allowed me to experience the personal satisfaction of the first two “d’s” in the therapeutics development triad; namely, discovery and development. But to achieve the last “d”; namely, delivery, I believe academic medical centers need to collaborate more with commercial biotech and pharma companies to achieve the ultimate goal of getting innovative therapies out to the general public. For example, in my leadership role at City of Hope, I oversee several resources that are actively collaborating with commercial entities in advancing new therapies and technologies, such as clinical-grade (GMP) manufacturing facilities which have some external clients, and we have recruited several members from industry to our internal committee which makes “go” and “no go” decisions about investment in our own products with commercialization potential.

Here is also where I see a lot of potential in Korea, with the growing excitement and corresponding investment in biotechnology that is taking place now. As a way to give back to my Korean heritage, I have a deep interest in making myself available to provide advice and guidance to the Korean biotechnology community to help catalyze growing collaborations with academic medical centers.

What would be your advice or comments for current medical students as well as those who aspire to become a doctor?

Dr. Kwak with his family at a family trip

Well, I think the wonderful thing about living in America is that you can still be recognized for your achievements, and so the advice that I give when I talk with young people is three things. The first is to make sure that in everything you undertake, you strive for excellence. Aristotle defined excellence as something that you do as a habit, so it’s not just a one-time event and it becomes a part of your core values. One component of excellence is the perseverance I spoke of earlier. Unfortunately, perseverance is becoming less popular among young persons – I see it even in my own children; one anecdote is that when I told my family about the TIME100 award, my second son’s response was, “Gee, that’s great Dad, but who would want to work on the same thing for 20 years?!” Second, seek out wise mentors. It’s very difficult to walk any road alone and I look at my own experience beginning with my high school summer internship experience as pivotal. I’ve had other mentors along the way at every step in my career that have really helped guide me, most recently Dr. Waun Ki Hong, Samsung Distinguished University Chair Emeritus Professor at MD Anderson Cancer Center. Third, especially for young families, my advice is to maintain proper perspective and be committed to your family. Several years ago, my wife and I authored a book (see photo) in Korea focused on the importance of teamwork in parenting. In it, we describe several examples from my own life making intentional choices to be a father that was involved in the lives of my four children. I can still recall deliberately turning off my mobile phone as soon as I arrived home each evening when our children were young to give them my undivided attention until they went to bed.

WKMJ has readers from more than 10 countries globally. Please share your final words with our readers.

Dr. Larry Kwak and his wife Ruth Kwak at TIME 100 Gala

I feel like the most fortunate person in this world, not only because of a wonderfully supportive wife and family, but also because I believe everyone has a purpose on this Earth, and my God-given, unique design happens to be my occupation. I love my job, because I wake up every morning anticipating that today is another day we might make a laboratory discovery that will make an immediate impact for cancer patients. In other words, I feel like I’m operating in my sweet spot, and I even get paid for it! One of my close friends, who founded a nonprofit leadership training organization, called Xealots, promotes the idea that we all have a universal calling; namely, to enhance the welfare of others. In the medical profession we benefit from having so many choices of primary care or specialties to choose among, so my hope for my fellow physicians of Korean heritage is that we all have maximum impact in our respective spheres of influence.

APRIL 3, 2017

Larry W. Kwak, MD, PhD

Vice President and Cancer Center Associate Director, Translational Research & Developmental Therapeutics City of Hope National Medical Center

Dr. Kwak is currently a Vice President and Cancer Center Associate Director of Translational Research and Developmental Therapeutics, Dr. Michael Friedman Professor for Translational Medicine, Director of Toni Stephenson Lymphoma Center at City of Hope National Medical Center. Dr. Kwak served as Head of the Vaccine Biology Section, Experimental Transplantation and Immunology Branch, at the National Cancer Institute (NCI) for 12 years. His NCI laboratory is credited with the pioneering bench-to-clinic development of a therapeutic cancer vaccine for B-cell malignancies, which was recently reported as positive in a landmark national Phase III clinical trial. From 2004-2014 Dr. Kwak served as Chairman of the Department of Lymphoma and Myeloma and Co-Director of the Center for Cancer Immunology Research at the University of Texas, M.D. Anderson Cancer Center in Houston, Texas, where he also held the Justin Distinguished Chair in Leukemia Research. Under his leadership, his department successfully captured extensive research support, including large team science grants, such as two SPORE grants in Lymphoma and Multiple Myeloma, respectively, from the NCI and a SCOR program project grant awarded by the Leukemia and Lymphoma Society. A committed physician, scientist, and mentor, his vision is to assemble and lead research teams to integrate basic discoveries from academic laboratories with translational clinical development to first-in-human clinical trials of novel “homegrown” therapeutics, such as next generation cancer immunotherapies. In 2010 Dr. Kwak was named to the TIME100, one of the world’s 100 most influential people by TIME magazine, for his 20 year commitment to the science of cancer immunotherapy. In 2016 he was awarded the Ho-Am Prize in Medicine for his pioneering research in cancer immunotherapy.