James P. Allison Institute
Unlocking the full potential of science and medicine for humanity
Exceptional Science. Enabling Cures.
Immunotherapy has transformed care for many patients with cancer, resulting in dramatic responses that last for years. However, not all patients benefit from immunotherapy. Our goal is to change that.
The James P. Allison Institute at MD Anderson is a visionary research and innovation hub created to conduct groundbreaking science that integrates immunobiology across all disciplines. With exceptional discovery, translational and clinical research, the Allison Institute will rapidly advance breakthroughs into novel and synergetic therapies that bring the benefits of immunotherapy to all patients.
The Allison Institute builds upon the legacy of its namesake, James P. Allison, Ph.D., who was awarded the 2018 Nobel Prize in Physiology or Medicine jointly with Tasuku Honjo, M.D., Ph.D., for fundamental discoveries that launched the field of cancer immunotherapy.
Launching a new era for immunotherapy
James P. Allison, Ph.D.
Director
Allison Institute
The immune system has endless possibilities for treating disease.
Empowering breakthroughs
Exceptional science drives our ambitious goals. We’ve built and innovative research model and established focused areas to accelerate progress.
Learn more about our research
Padmanee Sharma, M.D., Ph.D.
Director of Scientific Programs
Allison Institute
We will empower our researchers to make scientific breakthroughs.
Institute Members
Building on a deep commitment to discovery science, Allison Institute members will combine breakthroughs with insights from the clinic to advance treatment approaches that effectively integrate immunotherapy with conventional cancer therapies in synergetic combinations.
Learn about our membersThe Future of Immunotherapy
With a deeper understanding of immunology, we can develop synergetic combinations across the pillars of cancer care and offer truly individualized options for patients.
Read full articleLearn More About Immunotherapy
Which cancers can be treated with immune checkpoint inhibitors?
Updated June 28, 2024
Immunotherapy is a type of cancer treatment that does not target the cancer itself, unlike traditional treatments. Instead, immunotherapy trains the immune system to fight cancer. Several types of immunotherapy are now approved to treat a wide variety of cancer types.
“At times, our immune system can become tolerant to cancer for various reasons,” says Aung Naing, M.D., who leads an immunotherapy working group in MD Anderson’s Phase I clinical trials program. “With immunotherapy, we are trying to harness or reinvigorate the immune system so that it recognizes and attacks the cancer instead of being tolerant. These agents have transformed cancer care since the approval of the first immune checkpoint inhibitor for metastatic melanoma in 2011.”
What are immune checkpoint inhibitors?
Immune checkpoint inhibitors work by blocking checkpoint proteins – including CTLA-4, PD-L1 and PD-1 – on the surface of T cells. These proteins normally prevent T cells from attacking healthy cells, but treatment with checkpoint inhibitors unleashes the T cells to eliminate cancer cells more effectively. Approved checkpoint inhibitors include:
- anti-CTLA-4 therapies ipilimumab and tremelimumab
- anti-PD-1 therapies cemiplimab, dostarlimab, nivolumab, pembrolizumab, retifanlimab-dlwr and tislelizumab
- anti-PD-L1 therapies atezolizumab, avelumab and durvalumab
- anti-LAG-3 therapy relatlimab
Immune checkpoint inhibitors are one of several types of immunotherapy. Other forms include:
- Adoptive cellular therapies such as chimeric antigen receptor (CAR) T cell therapies, are immune cells taken from a patient or healthy donor and modified to boost their ability to eliminate cancer.
- Targeted antibodies are treatments that mimic naturally occurring antibodies from our immune system.
- Cancer vaccines train the body to recognize specific features of cancer and stimulate an immune response.
- Oncolytic viruses use engineered viruses to infect and destroy cancer cells.
- Immune system modulators, or cytokine therapies, use immune signaling compounds to stimulate immune activity.
Immune checkpoint inhibitors treat many types of cancer
Currently, the Food and Drug Administration (FDA) has approved immunotherapies to treat certain patients with the following cancer types. FDA approval is a carefully regulated process to ensure that medicines are safe and effective for patients.
- Alveolar soft part sarcoma
- Basal cell skin cancer
- B-cell lymphoma
- Bile duct cancer
- Bladder cancer
- Cervical cancer
- Classical Hodgkin lymphoma
- Colorectal cancer
- Cutaneous squamous cell cancer
- Endometrial cancer
- Esophageal cancer
- Head and neck squamous cell cancers
- Kidney cancer
- Liver cancer
- Lung cancer
- Melanoma
- Merkel cell cancer
- Mesothelioma
- Stomach cancer
- Triple-negative breast cancer
Additionally, some patients with advanced solid tumors and specific tumor characteristics, such as high microsatellite instability (MSI-H), mismatch repair deficiencies (dMMR), or high tumor mutational burden (TMB), may be eligible for treatment with certain immune checkpoint inhibitors, regardless of cancer type.
Immune checkpoint inhibitors may be used alone or in combination with other treatments, such as chemotherapy or targeted therapies. In many cases, patients must meet certain criteria to be eligible for these therapies. Keep in mind that the information shared here should not be considered medical advice.
"Immunotherapies are now not only being used to treat a large number of different cancers, but importantly, in some cancers like melanoma, they are now being used in earlier stages, either with a neoadjuvant approach (before surgery) or in the adjuvant setting. In both cases, the goal is to decrease the risk of cancer recurring at a later point. Other indications now include brain metastases," says melanoma medical oncologist Isabella Glitza Oliva, M.D., Ph.D. "Our research is continuing to push our understanding of why these successful therapies do not work in some patients and to enable us to find ways to help more patients."
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Q&A: Understanding our Immunotherapy platform
MD Anderson’s Moon Shots Program™ increases the speed at which our experts turn their research into new cancer treatment options for patients. At the core of this ambitious initiative are 10 research platforms, which provide the 13 disease-specific Moon Shots with specialized equipment, knowledge and data analysis tools.
To learn how the platform impacts our immunotherapy research and cancer treatment, we spoke with the Immunotherapy platform team, which is led by Jim Allison, Ph.D., and Padmanee Sharma, M.D., Ph.D.
What is immunotherapy?
Immunotherapy is a cancer treatment that uses the body’s own immune system to fight cancer.
One type of immunotherapy, called immune checkpoint inhibitors, provides lasting cures to a subset of patients with specific cancers, including:
- Bladder cancer
- Hodgkin’s lymphoma
- Kidney cancer
- Head and neck cancers
- Melanoma
- Merkel cell carcinoma
- Non-small cell lung cancer
Currently, not all patients benefit from immunotherapy, but through clinical trials, our experts are learning how to make this treatment more effective.
How does the platform contribute to our mission of ending cancer?
Our goal is to make immunotherapy a standard treatment option for many more types of cancers and patients. To expand the use of immunotherapy, we’re working to:
- identify the patients most likely to benefit from current immunotherapies,
- investigate why immunotherapy works for some patients and types of cancers but not others, and
- develop new immunotherapies and powerful combinations of existing therapies.
We’re testing tumor and blood samples taken from patients treated on immunotherapy clinical trials to achieve these goals.
The information we gather from analyzing these samples allows us to identify biomarkers that predict the likelihood that a patient will respond to currently available immunotherapies. This information can also guide our laboratory experiments aimed at finding new immunotherapy strategies.
What makes the Immunotherapy platform unique?
Our platform’s proximity to patients and our location within the world’s largest cancer center enables us to bring cutting-edge immunotherapy trials and treatments into the clinic at a relatively quick pace, which is extremely difficult to achieve in an academic research center.
Success in our work requires collecting a large number of tumor and blood samples from patients. In addition, some of the state-of-the art analyses we perform require very fresh samples, so it’s crucial that we have eligible patients nearby.
We also have a unique team of clinicians, physician-scientists, laboratory scientists and bioinformaticians – all of whom interact extremely closely. This collaborative effort provides real-time monitoring of patients across many immunotherapy clinical trials for several cancer types.
These advantages allow us to seamlessly move immunotherapy discoveries made in our research labs to our patients. The platform is also designed to tailor our research strategies in response to observations made in the clinic, so we can continuously improve the immunotherapies we’re bringing to patients.
We view this process as being both “from bench to bedside” as well as the reverse, from the clinic back into the laboratory. This is only possible in a limited number of cancer centers.
How is the platform advancing cancer immunotherapy?
Our platform leads path-changing studies that help uncover the complex biology of immunotherapies, in particular immune checkpoint inhibitors. Our accomplishments include:
- Discovering that the two primary immune checkpoint inhibitors used today, anti-PD-1 and anti-CTLA-4, affect the immune response in different ways.
- Conducting a clinical trial that led to the approval of anti-PD-1 therapy for the treatment of metastatic renal cell carcinoma, which is now the standard of care for these patients.
- Identifying how to predict whether a patient will respond to immunotherapy early during treatment of metastatic melanoma, which is vital to delivering the right treatment to the right patient as quickly as possible.
- Providing preclinical data that supported the initiation of a clinical trial combining anti-CTLA-4 and anti-PD-1 therapy for the treatment of castrate-resistant prostate cancer, which was previously considered a bad target for immunotherapy.
What’s next for the Immunotherapy platform?
We would like to see immunotherapy applied earlier in treatment, in combination with traditional therapies, such as radiation, chemotherapy and targeted therapies. These sorts of combinations are already showing promise of eliminating cancer throughout the body and making immunotherapy available for more types of cancers.
Request an appointment at MD Anderson online or by calling 1-877-632-6789.
Why doesn’t immunotherapy work for everyone?
In the last decade, immunotherapy has become a viable treatment option for many cancer patients. Unlike radiation and chemotherapy, immunotherapy does not target the cancer itself. Instead, it enables a patient’s own immune system to attack the disease. In most cases, immune-based treatments stimulate T cells, a specialized type of immune cell, to fight cancer.
Immunotherapy drugs called immune checkpoint inhibitors accomplish this by blocking checkpoint proteins that live on the surface of T cells and act as “brakes” to prevent the T cells from accidentally attacking healthy cells. Now a standard treatment for a growing list of cancers, checkpoint inhibitors have proven effective for treating several types of cancers, including melanoma, small cell lung cancer and non-small cell lung cancer, bladder cancer, kidney cancer, stomach cancer, liver cancer, head and neck cancers, and lymphoma.
“The survival outlook for patients with metastatic bladder cancer used to be less than one year, but I’m now seeing some of my patients coming back to the clinic over and over again, five years and longer,” says Padmanee Sharma, M.D., Ph.D., co-leader of MD Anderson’s immunotherapy platform. “It’s very rewarding to see that stage IV cancer patients can have hope.”
However, checkpoint inhibitors don’t yet work for everyone. Certain cancers, including pancreatic cancer, prostate cancer and glioblastoma, have been especially resistant to this approach.
“The idea that these agents work for some patients but not others is a huge research question we’re still trying to understand,” says Sharma.
Learning why cancers may not respond to immunotherapy
Jim Allison, Ph.D., discovered the first known immune checkpoint, CTLA-4, in 1995. By blocking CTLA-4 in the laboratory, Allison learned that T cells could be set free to attack cancer.
Allison’s work led to the development of the first immune checkpoint inhibitor drug, ipilimumab, which was approved by the Food and Drug Administration (FDA) in 2011 for treating advanced melanoma. Since then, the FDA has approved several new checkpoint inhibitors for a growing list of cancer types.
For checkpoint blockade to work, T cells must be present within a tumor and able to perform their jobs. A growing body of evidence has begun to clarify how some tumors resist this treatment approach, explains Sharma. These explanations include:
- Tumors can develop mutations or mechanisms that prevent T cells from penetrating the tumor.
- Tumors may respond to the immune system by turning down signaling pathways that normally stimulate T cells, thereby dampening the anti-tumor immune response.
- Higher numbers of suppressive immune cells, such as myeloid cells, may be present in some tumors, which counter the activity of T cells.
- In advanced cancers, the sites of metastasis have very different cellular environments than where the primary cancer developed. T cells may not function as well in those environments.
“The interplay between a tumor and the immune system is extremely dynamic,” says Sharma. “So strategies to make the best use of checkpoint inhibitors require a complex understanding of this evolving back-and-forth.”
That is precisely the goal of MD Anderson’s immunotherapy platform, an engine of the Moon Shots Program®.
Innovative research drives immunotherapy breakthroughs
Under the leadership of Sharma and Allison, the immunotherapy platform strives for a deeper understanding of how cancers respond to immune-based treatments, so that more patients can benefit.
Its research is built around a reverse translation concept, which was developed by Sharma in 2004 during the earliest immunotherapy clinical trials in bladder and kidney cancer. The platform’s research is designed to learn from patients in real time as they participate in the more than 100 clinical trials run through the platform. Patients are asked to provide samples before, during and after treatment so the research team can learn about the evolving immune response as it happens.
“As I explain to my patients what we’re trying to do – that we want to develop immunotherapy for more people – they understand the importance of the work,” Sharma says. “They know we may not find a cure for them, but their participation could lead to a cure for someone else, maybe even someone in their family down the road.”
New immunotherapy combination may yield new discoveries and treatments
The approach already has revealed important insights and led to the development of new combination treatments.
For example, an ongoing clinical trial with the Prostate Cancer Moon Shot® is showing promising early results by using multiple checkpoint inhibitors to treat advanced prostate cancer. Insights from this work also showed when prostate cancer spreads to the bone, it leads to massive destruction of bone tissue. This sparks production of a protein called TGF-β that can suppress the immune response. To better treat bone metastases, the platform is planning to launch a clinical trial that combines a checkpoint inhibitor together with a therapy that blocks TGF-β.
Platform researchers also worked with the Glioblastoma Moon Shot® team and learned that glioblastomas can overcome checkpoint blockade with another type of immune cell called macrophages. The researchers found that certain macrophages in the brain express high levels of the CD73 protein that thwart the activity of T cells in a tumor. Future studies will test a combination of checkpoint inhibitors and a CD73 inhibitor.
These projects are proving that the immunotherapy platform, an entity unique to MD Anderson, can drive important discoveries that will bring immunotherapy to more patients.
Request an appointment at MD Anderson online or by calling 1-877-632-6789.