The Comedy vs Cancer community is dedicated to accelerating blood cancer research at MSK.
Comedy vs Cancer Sets the Stage for New Blood Cancer Treatment
Comedy vs Cancer has raised more than $3 million to support five MSK physician-scientists who are improving CAR T cell therapy.
Fueled by Comedy vs Cancer support, medical oncologist Anthony Daniyan and his MSK team have developed a novel treatment for a type of blood cancer called acute myeloid leukemia (AML) that will soon be tested in a first-in-human clinical trial. If successful, the therapy could greatly improve care for people with blood cancers worldwide.
Targeting Acute Myeloid Leukemia with CAR T Cell Therapy
AML is one of the most common blood cancers in adults, but it can be very challenging to treat. Some AML cells are resistant to chemotherapy, and fewer than 30% of people with AML survive for more than five years after diagnosis, an outcome that has not improved in decades. In recent years, several successful blood cancer treatments have been developed based on a technology called chimeric antigen receptor (CAR) T cell therapy, an approach that uses a patient’s own immune system to fight cancer.
Car T Therapy
In CAR T cell therapy, immune cells are removed from a patient and re-engineered to bind to specific receptor targets on cancerous cells. When patients receive infusions of their modified T cells, the treatment activates a strong immune response to destroy cancer.
Jump-Starting the Immune System's Cancer-Killing Ability
Dr. Daniyan created a new treatment for AML that uses next-generation CAR T cells that are more efficient in detecting and destroying AML cells while sparing healthy cells. The modified CAR T cells, often called armored CARs, jump-start a patient’s immune system to boost cancer-killing activity in both the short and long term, much like a vaccine. Combined with chemotherapy, this technology could significantly increase the effectiveness of AML treatment.
To get this ambitious plan off the ground, Dr. Daniyan and his colleagues needed to engineer CAR T cells to target a protein called CD371 that is found on most AML cells, including those resistant to chemotherapy, but not on healthy cells. The team also had to make the CAR T cells produce the interleukin 18 protein, which acts as a strong signal to initiate and boost the immune response so that even the AML cells without CD371 are effectively destroyed.
How Donations to Comedy vs Cancer Accelerate Blood Cancer Research
Thanks to Comedy vs Cancer funds, Dr. Daniyan and his colleagues made important advances in the laboratory to create the building blocks for this strategy and clearly demonstrate the potential of the treatment. Based on their foundational research, the team was awarded a Specialized Program of Research Excellence grant by the National Cancer Institute to test the safety and effectiveness of this therapy in the laboratory.
Now Dr. Daniyan and his team are starting a phase 1 clinical trial for patients with AML that has not responded to other forms of treatment. MSK researchers are also working to adapt the new technology to target other blood cancers.
Dr. Daniyan gives full credit for his rapid progress to the strategic partnership between the Comedy vs. Cancer community and MSK’s physician-scientists.
Comedy vs Cancer Grant Recipients
Prasad S. Adusumilli, MD, FACS
Deputy Chief, Thoracic Service; Co-Director, Mesothelioma Program; Head, Solid Tumors Cell Therapy, Cellular Therapeutics Center
Dr. Adusumilli has demonstrated that CAR T cells can become functionally exhausted when they are used against solid tumors. In a recent Phase I study, he showed a stronger, more durable response to CAR T in some patients with advanced mesothelioma—by introducing a subsequent immunotherapy called a checkpoint inhibitor. Dr. Adusumilli hopes to initiate a new clinical trial that will combine both treatments in a single dose, to make CAR T even more effective and less toxic.
Kevin J. Curran, MD
Pediatric oncologist specializing in Allogeneic and Autologous Hematopoietic Stem Cell Transplantation for Children; Adoptive T Cell Immunotherapy
CAR T can be dangerously toxic—and is expensive. Dr. Curran is meeting these challenges with off-the-shelf CAR T cells that do not rely on manufacturing individual patient samples. His T cells are instead designed to only recognize a common viral signal found in cancerous blood cells. Ten patients have been treated with the therapy, and with encouraging results.
Anthony Daniyan, MD
Medical oncologist specializing in Adult Acute and Chronic Leukemias; Adoptive Cellular Therapy
Fewer than 30 percent of patients diagnosed with acute myeloid leukemia (AML) live beyond five years—because some AML cancer cells will resist chemotherapy. Dr. Daniyan has helped develop a CAR T cell that targets CD371, a molecule expressed on chemotherapy-resistant cells. The goal: to combine this CAR T treatment with chemotherapy to kill all AML cells, while sparing healthy cells.
Scott James, MD, PhD
Medical oncologist specializing in Stem Cell Transplantation; Leukemia; Multiple Myeloma; Myelodysplastic Syndrome (MDS); Lymphoma
AML has more variation in cancer targets than acute lymphoblastic leukemia, making it tougher to treat. Dr. James and his team have developed a patent-pending technology to generate multi-target CAR T cells to overcome this variation. They will move forward with producing these powerful CAR T cells, which may potentially eliminate 100 percent of AML cells in every patient.
Eric Smith, MD, PhD
Director of Clinical Translation, Cellular Therapeutics Center
Multiple myeloma is an incurable blood cancer. CAR T therapy that targets a protein, known as BCMA, helps some patients. But patients whose myeloma cells have little to no BCMA may relapse. Dr. Smith helped retool CAR T cells to target a different protein, GPRC5D, which is also prominent in myeloma cells. In laboratory models, it was effective. The next step: a clinical trial.