January 30, 2019
Dream Team targets T-cell lymphoma using CAR-modified cells in experimental therapy
BY Andrew Olin
A Dream Team assembled by Stand Up To Cancer will receive $8 million in funding to research the use of modified immune cells to fight the rare and often deadly T-cell lymphoma, a type of blood cancer. Investigators either will use a patient’s own T cells — the warriors of the immune system — or a type of immune cells known as natural killer (NK) cells — the first line of defense against cancer cells.
Both approaches will use chimeric antigen receptors (CAR) to activate the immune system to recognize and attack cancer cells. This is done by genetically modifying the T cells or NK cells to produce a protein (called a receptor) that recognizes another protein (called an antigen) on the surface of cancer cells. This recognition allows the modified immune cells to identify and destroy the cancer. The modified cells are then multiplied by the hundreds of millions and infused back into the patient to fight the disease.
Enlisting the body’s natural killers
Dream Team investigators from MD Anderson will focus on using CAR-modified NK cells to treat the cancer, which makes up less than 15 percent of non-Hodgkin lymphoma cases in the U.S., according to the American Cancer Society. Using immunotherapies to tackle T-cell lymphoma has presented the challenge of targeting cancer-causing T cells without harming other cells of the immune system.
Dream Team principal investigator Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson, and her team generate CAR-modified NK cells using umbilical cord blood from the institution’s umbilical-cord blood bank. The bank stores cord blood cells donated by mothers from Houston-area hospitals.
“For patients who lack sufficient T cells for CAR T-cell generation or cannot afford to forgo treatment for the time it takes to generate CAR T cells, we will turn to NK cells from cord blood to expand the use of CAR-directed therapy,” says Rezvani.
Unique advantages of NK cells
Because CAR-modified NK cells do not cause graft-versus-host disease, NK cells from a cord blood donor can be given to patients without fear of dangerous side effects. And using an experimental approach pioneered at MD Anderson, it’s possible to isolate, stimulate and engineer the NK cells in the lab, increasing their numbers by 2000 fold, according to Rezvani. Using this approach, more than 100 doses of CAR-NK cells can be generated and used to treat many patients.
These advantages can help decrease the cost of the treatment and increase its accessibility for patients.
“With the cord blood bank, we can have off-the-shelf products, NK cells that can be given to patients without a need to individualize them,” Rezvani says.
Researchers from MD Anderson, Baylor College of Medicine (BCM), the University of North Carolina-Chapel Hill (UNC-CH) and Wake Forest Comprehensive Cancer Center will collaborate on the project.
Stand Up To Cancer, a program of the Entertainment Industry Foundation created to encourage cancer research collaboration, and its scientific partner, the American Association for Cancer Research, announced the funding of the SU2C Meg Vosburg T-Cell Lymphoma Dream Team: Tailoring CAR-based Immunotherapy Strategies to T-cell Lymphoma on Jan. 28. The team will be headed by Helen Heslop, M.D., BCM, with Gianpietro Dotti, M.D., UNC-CH, as co-leader. Researchers from MD Anderson include Rezvani, Elizabeth J. Shpall, M.D., professor of Stem Cell Transplantation and Cellular Therapy and director of the Cell Therapy Laboratory and the Cord Blood Bank at MD Anderson, and investigator May Daher, M.D.
The Dream Team honors the memory of Meg Vosburg, a lifelong learner, educator and humanitarian, who died from T-cell lymphoma in 2018 at the age of 51.