Immunotherapy has revolutionized the way physicians treat patients with cancer. This form of cancer treatment aims to direct the immune system toward the rapidly growing tumor. As cancer progresses, tumor cells secrete different proteins and molecules to suppress the body’s immune system. Various mechanisms are responsible for doing this, including surface proteins on cancer that inactivate specific immune cells, known as T cells. Many cells are critical for the maintenance of a healthy body free from pathogens; however, T cells are a main cell type responsible for eliminating disease. The interaction between the surface proteins on both cancer and T cells suppresses T cell function. Immunotherapy functions to reactivate T cells and recognize the cancer. In this specific case, an immunotherapy designed to block surface marker interaction allows the T cell to find and target the tumor. Other forms of immunotherapy include engineered immune cells that are designed only to target cancer cells.
Specially engineered T cells produced to strictly target tumor cells are known as chimeric antigen receptor (CAR) T cells. This type of immunotherapy was first introduced in the clinic in the early 2000s. Specifically, physicians will take T cells from the patient and design the cells to recognize a specific cancer and reinfuse the engineered cells back into the patient. This form of therapy has been successful in many lymphomas, which are a type of hematologic or blood cancer. It is critical to identify a specific cancer target to avoid toxicity. Unfortunately, scientists are still developing this form of therapy to target more specific markers in different cancer types. Many cancer subsets, including acute myeloid leukemia (AML), do not have strong identifiable markers. Scientists are still investigating novel biomarkers to improve immunotherapy, including CAR T cell therapy.
A recent paper in Nature Cancer, by Dr. Naoki Hosen and others, describe a novel biomarker in AML, HLA-DRB1, and how it can be used to improve CAR T cell therapy. Hosen is a Professor in the Graduate School of Medicine, at Osaka University, Japan. His work primarily focuses on hematology or the study of diseases in the blood and cancer immunology. Specifically, Hosen’s work has led to the discovery of many different mechanisms in hematologic malignancies that can be exploited to improve CAR T cell therapy.
Many patients with AML are treated with an allogeneic hematopoietic stem cell transplantation (allo-HCT) from a healthy individual. Unfortunately, AML patients still have high recurrence of relapse. To improve therapeutic efficacy using CAR T cell therapy, Hosen and his team screened for biomarkers in human tissue by using antibodies. In this case, the team focused on the antibodies that reacted to surface proteins on AML cells only. Using this strategy, they found high affinity binding between the antibody, known as KG2032, and the marker, HLD-DRB1.
HLA-DRB1 is only present in the patient, not the donor’s stem cells from the transplant, which makes this marker ideal for patients that have relapsed. As a result, CAR T cells engineered to target HLA-DRB1 was found to elicit a strong immune response with minimal toxicity. These findings offer a promising therapeutic alternative. Scientists hope to move this therapy in the clinic and improve AML patient survival.
