Immunotherapy is a type of biological therapy that utilizes the patient’s immune system to fight cancer. Over the last decade, immunotherapy has been proven as a viable treatment for a range of cancers. One form of immunotherapy, called CAR-T cell therapy, has shown a high level of success for leukemia and lymphoma patients.

As you may have seen in the news in February, the second person in the world to receive CAR-T cell treatment has been cancer-free for 10 years. Doctors now consider him cured of chronic lymphocytic leukemia, a previously incurable blood cancer, because he has no cancer cells, and there are still CAR-T cells present and ‘on patrol’ in his body a decade after his initial CAR-T cell treatment. This is amazing progress!

The Morgan Adams Foundation researchers supported by donors have been advancing CAR-T cell work in leukemia and also expanding CAR-T cell therapy into other forms of pediatric cancer, including DIPG, ependymoma, and other types of brain cancer. They’ve also been working to apply CAR therapy to other areas of the immune system for solid tumor cancer types.

What is CAR-T cell therapy?

CAR-T cell therapy reprograms a patient’s T cells (the immune cells that protect the body) so that they will attack cancer cells.

The first step in creating a CAR-T cell treatment is identifying the critical antigen(s) that are present on the surface of the cancer cells. An antigen is a molecule that can bind to a specific antibody or T cell.

Once the antigen on the cancer cells is identified, a CAR-T cell is created by adding a new receptor for that antigen to the surface of the patient’s harvested T cells in the lab. That receptor is called a chimeric antigen receptor, or CAR. Combining the CAR with the patient’s T cells results in the desired CAR-T cell. 

The new CAR-T cells are returned to the patient’s body through an infusion. The CAR-T cells will then target and attack cancer cells in the body. CAR-T cells do this by latching onto the antigens on the surface of the tumor cells and killing them.

Your support has made several pediatric CAR-T cell projects possible, including:

  • Sujatha Venkataraman, PhD (University of Colorado Anschutz Medical Campus) is currently testing a novel CAR-T cell that targets an antigen found on DIPG and Ewing Sarcoma tumor cells. She is seeing very good in vivo results in both types of cancer.
  • Rajeev Vibhakar, MD, PhD, Eric Kohler, MD, PhD, and Sujatha Venkataraman, PhD (University of Colorado Anschutz Medical Campus) have developed a CAR-T cell that targets two antigens present on the surface of DIPG cells. This CAR-T cell is effectively targeting and killing DIPG tumor cells in in vivo lab studies.
  • Hannah Lust, MD (Lurie Children’s Hospital, Chicago) is analyzing blood samples from patients receiving CAR-T cell treatment for relapsed leukemia, lymphoma, and myeloma to determine the characteristics that make CAR-T cell therapy more or less effective. Blood samples are taken from patients at 5 time points during CAR-T cell treatment with the goal of tracking survival of CAR-T cells and the patient’s response to therapy.

How is CAR therapy being applied in new ways?

Solid tumors can present a challenge for CAR therapy because some types of immune cells may not be able to penetrate the tumor very well or may be inactivated by it. So, researchers in the Morgan Adams Foundation Pediatric Brain Tumor Research Program are investigating other ways to bring CAR therapies to kids with brain and other solid tumors.

For example, macrophages are an important type of immune cell. They are often best known as the ‘trash collectors’ of the immune system because they clean up the remains of what T cells attack and kill. Macrophages can also make tumors grow faster or slower, and are very efficient at eating tumor cells. Another key feature of macrophages is their unique ability to penetrate solid tumors, unlike some other types of immune cells that are kept outside the tumor.

Because macrophages are uniquely positioned for therapeutic uses in solid tumors, Siddhartha Mitra, PhD, Sujatha Venkataraman, PhD, and Eric Kohler, MD, PhD are working together to create CAR-engineered macrophages, also known as CAR-M cells. The team has shown that CAR-Ms will target and destroy specific cancer cells. They are currently working to demonstrate the effectiveness of CAR-M cells in the lab through in vitro testing on established pediatric brain tumor cell lines.

The potential of CAR-Macrophages to supplement CAR-T cell therapy for brain and other solid tumors is very exciting because more therapies are needed for hard-to-treat and highly malignant cancers that affect kids and teens.

Thanks to the support of generous donors, these ground-breaking research projects utilizing immunotherapy are possible.