James P. Allison


James P. AllisonAs a basic scientist, I have been fortunate to see my research findings translate into a powerful new potentially curative treatment strategy for cancer. The first patient I met was Sharon Belvin. I met her in 2006 at Memorial Sloan-Kettering Cancer Center (MSKCC). Jedd Wolchok, an oncologist at MSKCC, called and asked me to meet him in his clinic. There, he introduced me to Sharon Belvin, who was 24 years old and had been battling metastatic melanoma. Melanoma had invaded her brain, lungs, and liver. She was diagnosed at the age of 22 and had received multiple prior therapies but her cancer continued to grow and, when she was 23, she was told that she only had a few months left to live. But, as a last-ditch effort, she participated in a clinical trial of a then experimental drug, anti-CTLA-4. Within 3 months of starting treatment, her tumors shrank in size and then disappeared. In 2006, when I met her, it was her one-year anniversary of having completed the treatment. Her disease had responded to the treatment and she was considered in remission and possibly cured.

Sharon and I have become good friends. When her first child was born a few years later, she sent me pictures. Then pictures of her second child. She is now 13 years out from her battle with cancer and enjoying life with a vibrant family. I can’t help but cry whenever I tell this story. My meeting with Sharon was my first experience of how years of research as a basic scientist could have an impact on patients. Her experience, and those of many other patients with many types of cancer who have benefitted from this work, has provided inspiration to work to continue improving this therapy for the benefit of many more patients.

Early life, South Texas

I was born in 1948 in Alice, a small farming and oil town in the brush country of the Rio Grande Valley in South Texas. Those early years in Alice shaped who I would later become. Being in Texas, the whole town, including my two older brothers, was obsessed with football. But, I learned from a young age that being crushed under a pile of big sweaty boys on a hot Texas afternoon was not my idea of fun. My interests lay more in knowledge and playing at chemical and biological experimentation. If you couldn’t find me curled up with a book, I was probably in the garage dissecting frogs or making homemade bombs to test in the nearby woods.

My Dad was the old-fashioned kind of doctor that made house calls, and I would sometimes accompany him on his rounds around town. I think he was the first immunologist I met because, in the days before vaccines for measles, mumps, and other childhood diseases, he would take me with him so that I could be exposed to the other children who had these illnesses. It was his way of exposing me to the infectious agents while I was young so that I could develop immunity against these infections and avoid the dangers of contracting these illnesses as an adult.

My Mom died when I was 11 years old. This was my first loss to cancer. At the time I didn’t know it was cancer because people simply did not speak of such things during those days. All I knew was that my Mom was getting sicker and spending increasing amounts of time in bed. She would go to the hospital for treatment and come back with burns on her neck. I later learned that she was suffering from lymphoma and was receiving radiation therapy, the standard-of-care treatment at the time. One morning in summer of 1960, as I was leaving with family friends to go swimming, I was told to go back inside and see my Mom. I sat at her bedside and held her hand as she died. That was a defining moment in my early life. And then, not long after my Mom died, my uncle died from melanoma and another uncle later died from lung cancer.

Cancer treatment has always been in the back of my mind. Still, I can’t really say that the impact of cancer on my family motivated all that I would later do, but years later I knew that should the opportunity ever arise I would do all that I could to apply my work to curing cancer.

In high school in Alice, I was fortunate to have a few great teachers who went the extra mile to encourage me to do my best and to take advantage of available resources, some outside the reach of the standard curriculum. A counselor arranged for me to participate in special summer programs for talented students at University High School in Austin after the 8th, 9th, and 10th grades. The topics for the programs varied, but all focused on individual or small team conducted projects. These summers were invaluable in immersing me in new situations and broadening my perspectives. The summer after my junior year, I participated in a biology course sponsored by the National Science Foundation at UT Austin. The mornings during that summer were spent in lectures presented by Irwin Spear, a truly exceptional teacher who taught freshman biology at the University of Texas at Austin (UT Austin) during the academic year. And the afternoons during that summer were spent working in research laboratories. This was a life changing experience, and I began to seriously consider a career in science.

I had an unusual experience when I returned to Alice for my final year in high school, when biology was typically taught. I knew of Darwin and the Origin of Species from my reading, and Dr. Spear’s lectures had made it clear how essential the ideas of selection were to the understanding of many aspects of biology. So, when I feared that biology as taught in Alice was going to be completely devoid of any mention of these ideas due to the religious beliefs of the faculty, I refused to take the class. I could see no value in such a course. I told the school officials that teaching biology without Darwin was like teaching physics without Newton and would be a waste of time, and I would not enroll in the course. The response was that it was a required course and, without it, I would not be allowed to graduate (among other threats). Finally, a wise counselor proposed that I fulfill the requirement by taking a correspondence course from UT Austin. I successfully completed it and graduated high school in 1965.

The University of Texas at Austin: undergraduate and graduate training

I enrolled at UT Austin in the summer session immediately after high school graduation. Due to my summers in Austin, I never thought of going anywhere else. In accordance with my father’s hopes, I began as a premed student. However, I became dissatisfied with the rote memorization required in some of the pre-med courses. At the beginning of my second year, in order to make a little money and hopefully gain entrance into a research lab, I became a dishwasher for G. Barrie Kitto, a new assistant professor of biochemistry at UT Austin. Over time I was allowed to help with experiments, then do my own, and eventually have my own projects as an undergraduate researcher.

I gradually learned of a key difference between medical practice and laboratory research. I realized that a physician must have a brain full of facts which can be accessed rapidly to deal with emergency situations that may arise during patient care. Physicians have to be able to quickly analyze symptoms and implement a treatment plan. And physicians cannot be wrong. They must be accurate in order to help patients or, at least, avoid harming them. A scientist’s job is very different. A scientist is usually focused on interesting, and hopefully important questions, and generating experiments to test hypotheses. As a scientist, it is equally valid to prove the hypothesis true or false. That’s fortunate, because many of our hypotheses are wrong; in fact, if you are asking interesting questions, most of them are wrong. Being wrong can actually be a good thing, because the answers generated in disproving an incorrect hypothesis will help you and others to propose alternate hypotheses. Then, you go back to the lab to do more – hopefully better – experiments. I did not have the discipline to be a physician, so I chose to be a scientist and have more fun. My initial projects involved the biochemical taxonomy of sea urchins, sea cucumbers and starfish. These studies were interesting and taught me the importance of precision and rigor. My next major project focused on biochemical and serological characterization of bacterial asparaginases, which at the time were showing promise in the treatment of childhood leukemias.

In addition to my courses and laboratory studies, I truly enjoyed the music scene in Austin. These were wonderful years in Austin, especially with respect to the great music from Jerry Jeff Walker, Willie Nelson, and many others as well as the eclectic venues for hearing live music such as the Broken Spoke, Soap Creek Saloon, and, of course, the Armadillo World headquarters. Life was good!

It was also during my time at UT Austin that I took an undergraduate course in immunology taught by the late Professor Bill Mandy. Professor Mandy gave one lecture on T cells and I was hooked. T cells travel throughout the body seeking out cells that shouldn’t be there, such as virus-infected cells or even tumor cells, and T cells then eradicate these aberrant cells. Nothing was known about how T cells recognized foreign cells, or what regulated their proliferation and function, or virtually anything else. I was fascinated, and decided to devote my career to solving their secrets.

Scripps Clinic and Research Foundation: 1974–77

Professors Mandy and Kitto helped me get a post-doctoral appointment in Ralph Reisfeld’s laboratory at Scripps Clinic in La Jolla, California. I felt that this was a great choice because Scripps was a hotbed of research in immunology, and because Reisfeld had recently reported the isolation and initial characterization of human histocompatibility (HLA) antigens.

These molecules had been shown to be important in rejection of allografts in humans, and the mouse homologs, MHC antigens, were suspected as having a more general role in T cell recognition of other antigens. I was reasonably productive, and succeeded in obtaining some of the very first primary amino acid sequence information from both HLA class I and class II antigens.

But, once again it was not all work. One day we met Clay and Ailene Blaker, two expatriate Texans who moved to San Diego to surf and start a band, “Clay Blaker and the Texas Honky Band.” Clay was a singer/songwriter who wrote much of his own material. (One of his songs, “Lonesome Rodeo Cowboy” later became a hit for the country superstar George Strait). The music filled a void and reminded me of Austin. I had been playing harmonica for years, either tooting by myself or trying to play along with records by blues masters like Muddy Waters and Jimmie Reed, or with county outlaws like Willie Nelson and Waylon Jennings. I started sitting in with Clay’s band occasionally, and ended up becoming a regular band member, playing with the band at a country dive bar called the Stingaree every Tuesday night for more than a year. At one point the band decided to move back to Texas to play in the dance halls around Gruene and New Braunfels in the hill country of central Texas. I decided to keep my day job as a post-doctoral fellow, but Clay and Aileen were very successful, earning a strong following.

The University of Texas System Cancer Center – Science Park, Smithville: 1977–1984

I heard from a friend that the M. D. Anderson Cancer Center in Houston was opening up a small research institute in Smithville, which was about an hour away from Austin, and I secured a position as Assistant Professor. It was my chance to seriously devote my efforts to immunology, and also to get back to Austin.

It was a wonderful situation. We were in a bucolic setting in the Lost Pines area of central Texas, in the midst of a state park complete with a lake and hiking paths. The lab was about 7 miles from town, and we regularly saw deer, armadillos, and other wildlife on the laboratory grounds. There were only six faculty members and perhaps 50 staff in all. There was a grand esprit de corps, and we were accustomed to working together when extra hands were needed. We worked very hard, but also enjoyed the Austin music, exciting as ever, with many of the original artists still there, but also many new faces, like Stevie Ray Vaughn, Beto and the Fairlanes, and too many others to name.

Nominally the theme of the lab was carcinogenesis research, and my main project was to make monoclonal antibodies and use them to detect cell surface changes as liver cells become neoplastic. My colleague Douglas Hixson and I made good progress, but I was also free to begin my own efforts in T cell biology.

It was during my time at Smithville that I heard a lecture that Irv Weissman presented at the main campus in Houston that gave me some ideas, and led me to think of a series of experiments that might lead to identification of the T cell antigen receptor (TCR). The TCR was considered the “holy grail” of immunology at the time. Many high-profile labs and scientists were feverishly trying to find the TCR as its identification was key to unlocking the mysteries of T cells. T cells recognized MHC plus antigen that was found on antigen presenting cells (APCs), but the question remained: what was the specific molecule on T cells that enabled this interaction? I made a series of monoclonal antibodies that recognized clonotypic antibodies on mouse T cell lymphomas and I designed a set of biochemical experiments that, with the help of graduate student Bradley McIntyre, led to the identification of the protein structure of the TCR. This discovery led to a lot of notoriety and invitations to high level conferences.

After that, the race was on to clone the genes encoding the TCR. I spent a sabbatical as a visiting scientist in Irv Weissman’s lab in order to conduct experiments aimed at finding the genes for the TCR but, other brilliant scientists, including Mark Davis and Steve Hedrick, as well as Tak Mak, were the first to identify the genes for the TCR.

Nonetheless, my time in Irv’s lab opened a whole new world to me. I was invited to the University of California Berkeley to give a seminar and eventually I was offered a tenured-track position as a full Professor.

The University of California, Berkeley: 1984–2004

UC Berkeley is a marvelous place, teeming with bright, inventive people seeking knowledge. My time at UC Berkeley was notable for my interactions with many wonderful colleagues and students. It was a time of discovery, collegiality, long days working in the lab, and long nights partying with everyone in the lab. Max Krummel described it best by saying that the lab was filled with many personalities who enjoyed each other’s company so much that they worked together and had fun together, like a family, or like a pirate ship filled with great people having a great time, even as they continued to steer the ship in the right direction. We all worked hard to understand fundamental aspects of T cell activation and its regulation. These were exciting and heady times. I remember many scientific meetings, especially conferences at Asilomar where my lab members would lead intense scientific discussions during the day, and then celebrate at night by building a bonfire on the beach and dancing and singing until sunrise.

I also took on leadership roles for the first time at UC Berkeley, including chairing a fledgling new Division of Immunology in the Department of Molecular and Cell Biology, recruiting faculty as the department continued to grow, and building a supportive environment for junior scientists to succeed. I should point out that my strategy for mentoring consisted of protecting faculty from bureaucracy, providing resources, such as lab space, funding, and collaborations, encouraging people to pursue their scientific passion, and basically leaving them alone to pursue their goals, with some guidance when needed. I am very proud of the outstanding faculty that I hired, most of whom quickly rose to the top ranks of their fields. It was a joy to share data and interpretations of our research finding.

I also tried to inspire a culture of “work hard, play hard” in my lab and the department. New ideas and projects were always encouraged and drinks after work were also encouraged to discuss successes and disappointments. The bonds that were formed with people at Berkeley are lifelong because they were forged with a sense of camaraderie and shared vision.

My own scientific vision was clear at Berkeley: decipher the way in which T cell responses are regulated. The entire process of T cell responses starts with the TCR. The TCR is signal one and can be compared to the ignition switch of a car. It is needed to turn the car on and start the process of T cell activation, but we knew that it was not enough to get it going. A second, costimulatory signal, which could only be provided by specialized APCs such as dendritic cells was required. Without the second signal, T cells failed to proliferate and failed to respond to antigen, a state defined as anergy. In 1992, Fiona Harding in my lab showed that CD28, another protein on the surface of T cells, was sufficient and necessary to provide the second signal for full activation of naïve T cells and to prevent induction of anergy in T cell clones. CD28 can be compared to the gas pedal in a car, which allows the car to start moving.

Still, there was another important piece of the puzzle that had yet to be solved. Another receptor on the surface of T cells, named CTLA-4, had been found that bore significant homology to CD28. There was no scientific consensus on the potential function of CTLA-4 as most thought it was another positive costimulator. In 1993 and 1994, studies from my lab and Jeff Bluestone’s conclusively demonstrated that CTLA-4 is a negative costimulator that directly opposes CD28. CTLA-4 can be compared to the brake in a car, which acts to stop responses before they cause any damage.

Max Krummel worked tirelessly to conduct experiments focused on defining the role of CTLA-4. After we showed that CTLA-4 acts as an inhibitory receptor to control T cell responses, I immediately designed the experiments to test the idea that antibody blockade of CTLA-4 would lead to tumor eradication. I outlined the experiments to Dana Leach and he injected mice with tumors and then treated them with anti-CTLA-4. He showed me results from the first experiment in 1994 and I was absolutely blown away. The treated mice had all rejected the tumors. It was astounding. By blocking a single molecule, CTLA-4, we had reversed tumor growth and death! I knew that we had to immediately confirm the data by repeating the experiment in a blind fashion.

But, Dana was leaving on Christmas vacation to visit his family, and he did not have time to repeat the experiment. We agreed to do a blinded experiment where he injected a new set of mice with tumors and to treat half of them with anti-CTLA-4 and leave the other half untreated, without my knowing which group was which. He set up the experiment and left on his trip. I monitored the mice daily and recorded tumor growth on all of them. Initially, I was disappointed, since all of the mice demonstrated tumor growth equally. But then, around day 14, I noticed that some of mice had tumors that appeared to have stopped growing. Over the next few days it became apparent that the tumors were shrinking, and eventually disappeared, from some of the mice. It, of course, turned out that all the mice that eventually rejected tumor had received the anti-CTLA-4 antibody. It was another eureka moment! I knew that we had just figured out a way to treat cancer in patients. We conducted many other experiments in mice and confirmed our data over and over again with a variety of tumor types. We did not find any tumors that we could not cure with CTLA-4 blockade as monotherapy, or in combination with other agents, such as chemotherapy, radiation, vaccines, or local ablation.

We clearly demonstrated that CTLA-4 was an inhibitory signal on T cells, which was the first time that an inhibitory pathway had been described for T cell responses, and we showed that blockade of CTLA-4 could lead to tumor eradication. We tried to convince many different pharmaceutical companies to work with us over the next 5 years but had little success due to skepticism in the field after many failed clinical trials with other immunotherapy agents such as vaccines and cytokine therapies. Many people did not believe that it was possible to treat cancer with a drug that did not target tumor cells but instead targeted T cells. The field of oncology was focused on identifying genetic mutations in cancer cells and then targeting these specific mutations with drugs, even though such studies indicated that tumor mutations would continuously change and accumulate, which would lead to escape from the genetically-targeted drugs. I argued that the mutations would elicit T cell responses; therefore, we needed to target T cells to improve their responses against these tumor mutations. I repeated my claims that the immune system was a living and evolving system and if we allowed T cells to do their job, by removing the brake with anti-CTLA-4, the T cells would keep up with the evolving mutations in tumors so that T cells would eradicate the tumors and cure patients. My claims were met with skepticism over and over again. Luckily, my friend Alan Korman, convinced Nils Lonberg at the biotech company Medarex that it was a worthwhile endeavor to help with our project. Medarex had a technology well-suited to the task: mice whose antibody genes had been replaced by human genes and could directly produce human antibodies. Alan joined Medarex and with Nils quickly produced an antibody (MDX-CTLA-4 or MDX-010), which was renamed ipilimumab by the US Food and Drug Administration when it entered clinical trials.

As the inventor of CTLA-4 blockade I was not, of course, involved in the trials, but was kept informed of the main efforts. The early trials were promising, with objective responses in a Phase I trial of ipilimumab in melanoma, and in some small trials in prostate, kidney, and a few other types of cancer. While this generated considerable excitement, I heard troubling reports that ipilimumab failed with more stringent trials with progression-free survival (PFS) as the endpoint. I began to worry that the clinical investigators might not fully appreciate the biology of CTLA-4 blockade, and were treating it as a conventional cancer drug that kills cancer cells, rather than a drug that activates immune responses by removing inhibitory signals.

As much as I loved UC Berkeley, I began to feel the need to learn more about cancer clinical trials, which was not possible there. In 2003 Harold Varmus and Thomas Kelly offered me the opportunity to lead the Immunology program at the MSKCC in Manhattan, and I accepted, not only to develop a world-class immunology program, but also to be close to the anti-CTLA-4 trials, many of which were being conducted at MSKCC.

Memorial Sloan-Kettering Cancer Center: 2004–2012

I arrived in Manhattan during the summer of 2004 with most of my laboratory intact. Over the next 8 years, I did my best to help Thomas Kelly hire a cadre of the best immunologists that we could, and I feel that we succeeded in building a truly spectacular group of basic immunologists involved in a variety of studies relevant to the cancer problem. My own lab continued to study mechanisms of checkpoint blockade, new combinations that enhanced efficacy, and to identify and characterize new checkpoints that might also be targeted to improve the efficacy of checkpoint blockade.

One of the biggest pleasures of being at MSKCC was getting to know Dr. Lloyd Old, considered by many to be the father of modern tumor immunology and immunotherapy. I was very lucky to have him as a friend and mentor. One of Lloyd’s mantras that still resonates with me today: “We must learn from each and every patient!” Lloyd and Dr. Padmanee (Pam) Sharma, an oncologist who was near completion of her postdoctoral studies as an immunologist with Lloyd, had been consulting with the Medarex team in designing and conducting trials with ipilimumab.

Sharma’s experience in patient care, clinical trials, and immunology were impressive, and she left MSKCC to begin her independent career at the University of Texas MD Anderson Cancer Center in 2004. We agreed to stay in touch and try to work to better understand how CTLA-4 blockade impacted patients’ immune responses.

At MSKCC I worked closely with Dr. Jedd Wolchok, who was the clinical investigator leading the anti-CTLA-4 trials in patients with metastatic melanoma. Jedd and I worked with Bristol-Myers Squibb (BMS), including Dr. Rachel Humphrey, who was leading the clinical trial development of anti-CTLA-4 with the Medarex team. Rachel and I became colleagues and good friends, and even band members in a new band that we established with Tom Gakjewski (University of Chicago) and Patrick Hwu (MDACC), both of whom were working in the emerging field of immuno-oncology. Naturally we agreed to name the new band “The Checkpoints”. The band has grown to include a full horn section with Jedd on tuba and has a fairly large repertoire of rock and roll, blues and pop songs. We have entirely too much fun playing at scientific meetings! Again, the theme of “work hard, play hard” permeated my years at MSKCC.

During this time, BMS faced a critical decision that would determine the fate of immune checkpoint blockade as a strategy for cancer therapy. A Phase III registration trial of ipilimumab in metastatic melanoma with the endpoint of PFS had begun. While this endpoint was reasonable for cytotoxic drugs, it was not clear that it was appropriate for CTLA-4 blockade. Our work in mouse models indicated that anti-CTLA-4 works at the time of T cell priming, and allows the expansion of T cells to large numbers to deal with the tumor mass. In our preclinical studies in mice, the tumors almost always grew before they regressed. Of course there are many reasons why the details of mouse results might not reflect those of clinical studies. A more serious concern was that PFS had been one of the endpoints evaluated in many of the earlier trials, and many of the earlier trials had failed to identify clinical benefit using the PFS endpoint. Also, a trial by Pfizer with a different anti-CTLA-4 antibody had failed. The choice for BMS was to shut down their trial with anti-CTLA-4, or incur the tremendous additional costs of a trial with the endpoint of overall survival, which would likely take many more years to complete. The pressure to stop the BMS Phase III anti-CTLA-4 trial was tremendous, but clinical investigators, including Pam Sharma and Jedd Wolchok, and some of the BMS team members, including Rachel Humphrey and Elliott Sigal, championed keeping it open, and prevailed.

While waiting for the next few years for the outcome of the Phase III trial, we all continued our studies. We were invited to many scientific meetings where we would meet with other researchers in the field, including Pam, to share our data at podium presentations during the day and over drinks at the bar in the evenings. It was an exciting time as we all shared our experiences from different institutions and different clinical trials. Those involved in research related to CTLA-4 became a growing community of investigators. Anti-CTLA-4 was working for patients with metastatic melanoma in early clinical trials and, in 2006, Pam shared with us that she was conducting pre-surgical studies in patients with bladder cancer and she observed tumors disappearing in those patients as well.

She also performed novel immune monitoring studies on the tumor and blood samples that she took from patients and identified CD-4 T cells expressing inducible costimulator (ICOS) as a critical component of the anti-tumor responses. It was impressive to me that she could design studies that provided both significant clinical data and novel insights into the scientific mechanisms underlying responses with anti-CTLA-4. I asked her to collaborate with Jedd and myself on the involvement of the ICOS+ T cells in melanoma, and we found in those studies, and in others, that the novel ICOS+ T cells play a causal role in the therapeutic effect of antiCTLA-4 both in patients and animal models.

Our team of investigators expanded to include many more people over the years. The field of cancer immunotherapy exploded as a result of the clinical success of anti-CTLA-4, which opened a new field termed immune checkpoint therapy. Scientific meetings had more and more talks related to immune checkpoint therapy. Immunotherapy sessions at meetings, which previously had less than 50 people in attendance, required larger and larger rooms as hundreds and then thousands of people attended. Cancer immunotherapy went from a fringe science to events that were compared to sold-out rock concerts, which was fitting since our band played after some of the scientific meetings to an equally growing fan base.

The results of the Phase III trial of ipilimumab were finally presented in the Plenary Session of the annual meeting of the American Society of Clinical Oncology (ASCO) in June of 2010. The audience, used to many years of failure of immunotherapy trials presented to tiny audiences, was electrified: ipilimumab was successful in extending the median overall survival of melanoma patients. This had never before been reported in trials of melanoma patients for any other agent. Several years later, when sufficient data were available, a retrospective study showed that thousands of patients with metastatic melanoma who had undergone a single course of treatment, typically consisting of 4 doses of therapy over 3 months, were alive 10 years later.

In March of 2011, I was attending a small Banbury meeting on melanoma at the Cold Spring Harbor Laboratories and I was nervously checking my email because it was the day that the US Food and Drug Administration was scheduled to announce its decision on ipilimumab. At about 11:30AM I received an email from Alan Korman with a picture of of him and Nils Lonberg sharing celebratory drinks of whiskey! This was my first indication that the news from the FDA had been positive and anti-CTLA-4 had become an approved standard-of-care treatment for patients with melanoma.

I’ve met many patients who were successfully treated with anti-CTLA-4, including Sharon Belvin who became a close friend over the years. Unfortunately, during my time at MSKCC, I also experienced many losses, including the death of my brother Mike in 2005, and my friend, and mentor Lloyd Old in 2011, from metastatic prostate cancer. AntiCTLA-4 led to tumor eradication and even cures in some patients but not in all patients. And, for patients with certain tumor types, such as prostate cancer and pancreatic cancer, anti-CTLA-4 did not seem to work at all. I was familiar with Pam’s work focused on evaluating patients’ samples from clinical trials to identify mechanisms of response and resistance to anti-CTLA-4 therapy, including a trial in prostate cancer patients that she designed in 2009, and I was convinced that we needed to expand these studies to build a larger program.

It is safe for me to say that the collaborations with Pam and I had over the years had clearly become a highlight in both my scientific career and my personal life. With time we developed a remarkable level of mutual respect and admiration and love. Eventually we became partners not just in science, but also in life.

University of Texas MD Anderson Cancer Center: 2012–present

At MSKCC, my lab had continued exploring ways in which to improve anti-tumor responses with anti-CTLA-4 treatment. We performed many experiments including combinations with chemotherapy, radiation therapy, cryoablation and with other immune checkpoint agents. After anti-CTLA-4 was shown to have some clinical success in the early clinical trials, many investigators searched for other potential inhibitory molecules. These studies led to identification of the PD-1/PD-L1 pathway as another inhibitory pathway that regulated T cell responses. Clinical trials also led to FDA-approval of anti-PD-1 and anti-PD-L1 antibodies as treatments for patients with cancer. Our lab also showed that combination therapy with anti-CTLA-4 plus anti-PD-1 improved anti-tumor responses in mice.

These data were also translated to the clinic and the US FDA approved combination therapy with anti-CTLA-4 plus anti-PD-1 for patients with melanoma and patients with kidney cancer. Again, these studies demonstrated that some patients responded to therapy but, some patients did not. I knew that we were at the tip of the iceberg in terms of unleashing the full power of the immune system to treat cancer and I wanted to delve deeper by building a translational research program to quickly move between the lab and the large number of clinical trials with immune checkpoint therapy that had emerged as a result of the success with anti-CTLA-4. I decided to move to MDACC to build the Immunotherapy Platform with Pam.

In 2013, I left MSKCC to partner with Pam, who was already conducting mechanism-based clinical trials to study immune responses in patients who receive the immune checkpoint agents. I am Chair of Immunology at MDACC. I’m also continuing to work on fundamental immunologic mechanisms in my lab and we recently demonstrated significant differences between CTLA-4 blockade and PD-1 blockade. In addition, based on Pam’s clinical and laboratory studies, which had already established a translational research program for genitourinary malignancies, I worked with institutional leadership to expand this translational model to the entire institution, encompassing 18 different departments and multiple tumor types. Pam and I established and lead the Immunotherapy Platform. Partnering with physicians from around the institution, we obtain and analyze tumor samples from patients on treatment in clinical trials with immune checkpoint inhibitors or other combination immunotherapy studies. We’re currently involved with immune monitoring studies from over 100 clinical trials. Our goal is to gain mechanistic insight into the therapies that will allow us to develop rationally based combination therapies to bring the benefits of immuno-oncology to more patients with more types of cancer with the goal of obtaining cures.

Of course, my time at MDACC also reverberates with my motto, “work hard, play hard”. I have a second band in Houston called The CheckMates. I continue to play harmonica at events with both The Checkpoints and The CheckMates. I’ve also had the privilege to play with Willie Nelson and Mickey Raphael, who I consider to be the greatest harmonica player on the planet. I continue to follow my passion for science and for life, and I’m truly grateful for the privilege of having a lifetime spent studying fundamental issues of biology that interested me, and that turned out to be of benefit to people with cancer.

From The Nobel Prizes 2018. Published on behalf of The Nobel Foundation by Science History Publications/USA, division Watson Publishing International LLC, Sagamore Beach, 2019

This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/ Nobel Lectures/The Nobel Prizes. The information is sometimes updated with an addendum submitted by the Laureate.

Copyright © The Nobel Foundation 2018

To cite this section
MLA style: James P. Allison – Biographical. NobelPrize.org. Nobel Prize Outreach AB 2023. Mon. 11 Dec 2023. <https://www.nobelprize.org/prizes/medicine/2018/allison/biographical/>

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