The Nobel Prize in Physiology or Medicine has been awarded today to two scientists whose groundbreaking work led to the development of a class of immunotherapies called checkpoint inhibitors that work by releasing the brakes on the immune system.
James P. Allison, Ph.D., chair of department of immunology at MD Anderson Cancer Center in Houston and director of the Cancer Research Institute Scientific Advisory Council, and Tasuku Honjo, M.D., Ph.D., of Kyoto University School of Medicine for Advanced Study and a professor in the department of immunology and genomic medicine at Kyoto University in Japan, shared the honor.
These game changing therapies, now approved for multiple types of cancers, work by blocking certain proteins that suppress the immune system and allow the cancer cells to hide from the body’s T cells. By blocking the ability of these proteins on the T cells to bind to other proteins on the surface of tumor cells, the T cells are unleashed to track down and kill the cancer cells.
The first immune checkpoint inhibitor was FDA approved in 2011 to treat metastatic melanoma. This approval was followed by others to treat solid tumors such as metastatic non-small-cell lung cancer, squamous cell carcinoma, head and neck cancers, bladder cancer, kidney cancer, urinary tract cancer and others. The first immune checkpoint inhibitor for patients with a blood cancer was approved in 2016 for treatment of Hodgkin lymphoma (HL).
LLS supported key laboratory work to indicate that one of the checkpoint inhibitors might work well in this disease…and it did! There are now two approved checkpoint inhibitors to treat HL, one of which is also approved to treat a rare type of non-Hodgkin lymphoma. The Leukemia & Lymphoma Society (LLS) has, and continues to fund multiple research projects pursuing further understanding of the utility of checkpoint inhibitors in several types of blood cancers.
Allison’s discoveries led to the development of the first FDA-approved checkpoint immunotherapy, the anti-CTLA-4 antibody known as ipilimumab (Yervoy®).
Honjo discovered another immune blocking protein called programmed cell death protein-1 (PD-1). FDA-approved therapies that target PD-1 Include pembrolizumab (Keytruda®) and nivolumab (Opdivo®).
While this particular approach to immunotherapy got its start in the solid tumors, the concept of boosting and deploying the immune system to fight cancer has its roots in blood cancer research, beginning with bone marrow cell transplantation in the 1950s. LLS has supported two other foundational concepts in immunotherapy. The first one is the use of antibodies that bind to and disable specific proteins on the surface of the cancer cells, thus allowing the immune system’s cells to swarm and kill the cancer cells.
These immune checkpoint inhibitors in today’s news are a type of antibody therapy. The first antibody therapy approved for use in cancers was rituximab (Rituxan ®), approved in 1997 to treat non-Hodgkin lymphoma, and later for chronic lymphocytic leukemia (CLL) and autoimmune diseases such as rheumatoid arthritis. This was quickly followed by the approval of trastuzumab (Herceptin ®) in 1998 by the FDA. Since then, dozens others have followed for multiple types of cancers.
The second effort is to genetically engineer T cells to selectively identify tumor cells and become super-activated upon binding to the tumor cells. This treatment, chimeric antigen receptor (CAR) T cell therapy, was developed for blood cancers over the past 20 years and is now approved to treat acute lymphoblastic leukemia and some types of large B-cell non-Hodgkin lymphoma.
Immunotherapy has become a mainstay therapy to treat blood cancers and other cancers. We salute Drs. Allison and Honjo for their contribution to science and medicine. Your support will enable LLS to maximize the impact of this work to its fullest in this rapidly emerging field of discovery.
What does a mother of three small children do when she hears the words, “You have cancer?” For Sonia Dolinger, her first reaction was to hide in her closet, crying into a pillow so her children couldn’t hear. “It was the scariest moment in my life,” said Sonia. “I mourned the high school graduations and weddings I’d miss, and the chance to have grey hair and one day be called grandma.” She was diagnosed with chronic lymphocytic leukemia (CLL).
Soon, Sonia realized that if she was going to beat this disease, she needed to stop her wallowing and be her own best advocate. She embarked on an educational journey of self-discovery and cancer research and began reading through patient stories on The Leukemia & Lymphoma Society’s (LLS) online forums.
“I read of new treatments that were being tested in clinical trials, and I followed these patients’ remarkable journeys,” said Sonia. “I learned about clinical trials for CLL, and I gained something paramount to any survival story, hope!”
So when Sonia heard of a clinical trial looking for patients needing new treatment options, she enrolled without hesitation.
Today, Sonia is in remission. She currently works with LLS as a fundraising campaign manager and continues to give back.
This fall, 1 million friends, families and co-workers nationwide will gather together to celebrate, honor and remember those touched by cancer at LLS’s Light The Night Walks. Survivors, like Sonia, celebrate within the survivor circle while the white beam of hope reaches up to the sky, illuminating the darkness. Supporters participate in honor of survivors and the strides LLS is making to find cures. Those we have lost are commemorated at the Remembrance Pavilion. The light and warmth generated delivers hope in time of despair, community in place of loneliness and lifesaving research & support for cancer patients and their families.
“Thanks to the support from the LLS, many of these drugs have gone from a twinkle in a scientist’s eye to saving lives!” said Sonia. “As an employee of LLS I’m thrilled to see and hear from patients frequently, many of whom have renewed hope in their fight against cancer.”
As LLS’s National Presenting Sponsor of Survivorship and Hope, Pharmacyclics and Janssen are committed to working with LLS through its Light The Night fundraising campaign to shine a spotlight on what it means to be a cancer survivor.
Eight-year-old Kaitlyn Johnson has had to deal with cancer for the majority of her young life. In fact, she was only 18 months old when she was diagnosed with acute lymphoblastic leukemia (ALL), the most common cancer among children and young adults. Her young life was quickly consumed with cancer treatments, doctors’ visits, and hospital stays. Throughout this time, Kaitlyn was brave, positive and continued to pursue her passion for dancing – no matter the location.
When she was first diagnosed, her parents, Mandy and James, made a decision that they would make this situation as positive as it could be. The family dressed up together before going to the hospital, made friends with all the people who they trusted with her care, and found small ways to make each moment positive.
Kaitlyn’s perspective is incredibly unique. A hospital visit is not feared, but it is a place where she can say hello to all her friends – from her friends who are patients, other families, nurses, doctors, security guards, to her therapy dog.
“As a parent, if your child is scared you want to be who they reach to. You’re conditioned to think that you’re the brave one,” said James. “But, when your kid touches your hand in that moment of fear and comforts you, you realize that they are the reason you’re strong.”
After three years of chemotherapy, the treatment was not working. Mandy and James had long discussions with Kaitlyn’s doctor who suggested that they enroll Kaitlyn in a clinical trial for a new immunotherapy. The revolutionary treatment, called CAR T-cell immunotherapy, had showed promise for other young children like Kaitlyn. The process was extremely unique and innovative – the doctors would remove Kaitlyn’s T-cells, the soldiers of her immune system, and reengineer them so that they could fight her cancer.
Today, Kaitlyn is now cancer free.
One Child Too Many
Unfortunately, not all stories of childhood blood cancer patients have a happy ending like Kaitlyn’s. A staggering forty percent of all pediatric cancers are blood cancers, and although survival rates have improved dramatically in recent decades, every young life lost to blood cancer is one too many. Since childhood cancers are biologically distinct from adult cancers, the way children respond to treatment is unique and dedicated pediatric research is needed to understand the molecular underpinnings of these diseases, identify appropriate dosages and evaluate the long-term impact of treatment.
Since LLS was founded in 1949, the median five-year-survival rate for children with acute lymphoblastic leukemia (ALL), the most common type of cancer to impact children, has improved from 5 percent to approximately 90 percent. But there is still much more to do.
Although survival rates have improved dramatically for children with ALL, children with other types of blood cancers, such as acute myeloid leukemia (AML), still face a difficult prognosis. Further, the lifelong impact of childhood cancer treatment can include severe physical and cognitive impairments, secondary cancers, and a range of ailments that the medical community is only beginning to understand.
That’s why LLS has committed to more than doubling our investment in pediatric research over the next five years. We are committed to investing $20 million in pediatric cancer research over this time in programs spanning the spectrum from basic science to translational research and clinical trials. We have convened a team of leading pediatric physicians and scientists to investigate the feasibility of launching a multi-site precision medicine clinical trial in pediatric leukemia. We’ve also set an ambitious goal of sequencing the genetic profiles of every child with leukemia in order to facilitate faster and more precise research into the unique molecular drivers and pathways of pediatric cancers. Our ultimate goal is to bring cures to children faster and deliver the promise of precision medicine to children with leukemia.
At the same time, we plan to expand the education and support we already provide to children with cancer and their families, including clinical trial enrollment, financial assistance, and local support groups. Through our advocacy efforts, we will continue to advocate for cures and ensure these children are able to access lifesaving treatment.
For education programs on childhood cancer, click here.
After three years of chemotherapy, the treatment was not working. Mandy and James had long discussions with Kaitlyn’s doctor who suggested that they enroll Kaitlyn in a clinical trial for a new immunotherapy. The revolutionary treatment, called CAR T-cell immunotherapy, had showed promise for other young children like Kaitlyn. The process was extremely unique and innovative – the doctors would remove Kaitlyn’s T-cells, the soldiers of her immune system, and reengineer them so that they could fight her cancer.
Although survival rates have improved dramatically for children with ALL, children with other types of blood cancers, such as acute myeloid leukemia (AML), still face a difficult prognosis. Further, the lifelong impact of childhood cancer treatment can include severe physical and cognitive impairments, secondary cancers, and a range of ailments that the medical community is only beginning to understand.