The US Food and Drug Administration (FDA) recently approved the first adoptive cell therapy for the treatment of cancer.1 Tisagenlecleucel is a chimeric antigen receptor (CAR)-T cell therapy approved for some pediatric and young adult patients with acute lymphoblastic leukemia (ALL).
“Adoptive cell therapies rely on the immune system to fight cancer instead of cytotoxic drugs,” said Barbara Savoldo, MD, PhD, of the Lineberger Comprehensive Cancer Center at the University of North Carolina in Chapel Hill. “With cancer, the tumor has escaped the immune system’s ability to fight infection, but adoptive T cell therapy re-empowers and exploits the immune system to fight the tumor.”
T cells can be redirected toward cancer antigens through genetic manipulation that allows for re-infusion of a tumor-specific CAR or T cell receptor (TCR). In a recent review, Dr Savoldo and a co-author discussed some of the most recent advances in the use of adoptive cell therapy for hematologic malignancies.2
Research into the use of adoptive cell therapy is much further along in the field of hematologic malignancies compared with solid tumors. According to Dr Savoldo, the nature of hematologic malignancies does seem to lend itself more naturally to this type of therapy.
“In the case of ALL, and probably other hematologic malignancies, the tumor cell is circulating in the blood stream or in tissues that are accessible to where adoptive T cells would normally circulate,” Dr Savoldo said. “This means there is a more natural path for the cells to find the tumor and kill it.”
Many of the early successes seen with adoptive cell therapy with CAR T cells has been in hematologic malignancies targeting CD19, which is expressed by B cell derived leukemias, and non-Hodgkin lymphomas. Trials of the recently approved tisagenlecleucel showed complete responses in about 80% of patients with relapsed or refractory ALL. Responses rates in trials of CD19-targeting CAR T cell therapy in patients with chronic lymphoblastic leukemia (CLL) or non-Hodgkin lymphoma have been slightly less successful.