Investigating CAR T Cell Therapy as a Bridge to Transplant

May 6, 2024 
This page was reviewed under our medical and editorial policy by Leslie Popplewell, M.D., Hematologist and Medical Director of Hematology and Blood and Bone Marrow Transplant, City of Hope Atlanta

Immunotherapy strengthens the immune system to help it shrink or eliminate tumors. Many experts call it the “fifth pillar” of cancer treatment — after chemotherapy, surgery, radiation therapy and targeted therapy — because it may be highly successful in fighting advanced cancer and, in some cases, offer results that last for years.

There are many kinds of immunotherapy, including immune checkpoint inhibitors, bone marrow transplants and CAR (chimeric antigen receptor) T cell therapy. While these treatments may be successful alone, CAR T cell therapy combined with a transplant may lead to even more improved outcomes. City of Hope^®, a global leader in immunotherapy, is spearheading the charge to investigate how this novel treatment method may benefit patients with blood cancers, also called hematologic malignancies, such as leukemia and lymphoma.

Current Treatments for Leukemia and Lymphoma

Bone marrow transplant and CAR T cell therapy are two leading treatment options for people with lymphoma and leukemia.

CAR T cell therapy trains the body’s immune system to detect and combat cancer while it scans the body for foreign invaders. Usually, it detects these perceived threats by identifying antigens, which are substances on a cell’s surface. When it discovers a threat, it enlists a type of white blood cell called T cells to fight it. These cells have various kinds of receptors, each of which is designed to attach to a specific type of antigen. Cells in the body also have antigens, but the immune system typically doesn’t perceive these as dangerous. Because cancer cells aren’t foreign substances, T cells may not have the correct receptors to bind to them.

CAR T cell therapy involves removing T cells from the patient’s bloodstream and combining them with the chimeric antigen receptor. Different types of cancer have different antigens, and each CAR is designed to bind to a certain one. For instance, some types of leukemia and lymphoma contain the CD19 antigen, so CARs that fight these cancers attach to the CD19 antigen but not others.

After the T cells have been modified, the doctor reintroduces them to the patient’s body.

Bone marrow transplantation involves replacing another kind of cell, known as stem cells. There are multiple kinds of stem cells throughout the body, and each type serves a singular purpose. Hematopoietic stem cells are found in bone marrow, peripheral blood and umbilical cord blood. They have the ability to multiply and change into different types of blood cells, including white and red blood cells and platelets.

Cancers like leukemia and lymphoma, along with treatments such as chemotherapy and radiation therapy, may damage hematopoietic stem cells and inhibit the body’s ability to produce new blood cells. A bone marrow transplant may help restore this function.

There are two types of bone marrow transplants. One involves infusing a patient’s bone marrow with stem cells from a bone marrow transplant donor–this is called an allogeneic transplant. The other, an autologous transplant, consists of doctors retrieving stem cells from the patient before administering chemotherapy or radiation therapy and putting them back into the patient’s body afterward.

Both types of transplants allow doctors to deliver higher doses of radiation and chemotherapy. Donor transplants also work via the graft-versus-tumor or graft-versus-cancer-cell effect, which is when white blood cells from the donor attack cancer cells.

City of Hope CAR T Cell Expertise and Research

City of Hope solidified its position as an immunotherapy pioneer in the 1970s, when Stephen J. Forman, M.D., made groundbreaking developments in bone marrow transplantation. In the decades that followed, City of Hope established itself as a global leader in stem cell transplantation with one of the nation’s largest and most successful bone marrow transplant centers in the nation today.

Since the 1990s, City of Hope has been a nationally recognized leader in CAR T cell therapy. The institution developed an innovative, proprietary CAR T cell technology to treat glioblastomas that’s now being used in preclinical and clinical trials nationwide. It was recently demonstrated to show how CAR T cell therapy may be used to fight treatment-resistant ovarian cancer.

Currently, the institution is engaged in more than two dozen clinical trials to investigate how CAR T cell therapy may improve outcomes for patients with other cancers, such as prostate cancer, glioma, pediatric brain cancer and blood cancers. Some of its most exciting studies involve using CAR T cell therapy in the treatment of high-risk and recurring blood cancers, such as leukemia and lymphoma, as well as the rare disease amyloidosis.

City of Hope scientists have also been at the forefront of CAR T cell therapy and bone marrow transplant research to evaluate how using these therapies together may lead to improved outcomes for some patients with advanced leukemia and lymphoma. CAR T cell therapy alone is appropriate for many patients, but research indicates combining the two treatments may offer improved results for some patients.

With its sterling, decades-long track record, world-class campus and comprehensive, patient-centered approach to research and care, City of Hope is uniquely positioned to lead this potentially lifesaving investigation.