Marco L. Davila, MD, associate attending physician in the Department of Blood & Marrow Transplantation and cellular immunotherapy medical director of the Cell Therapy Facility at the Moffitt Cancer Center, discusses his research in off-the-shelf, allogeneic T-cell immunotherapies. He discussed the next-generation chimeric antigen receptor (CAR) T-cell technologies.
“The next generation of CAR T cells are going to be optimized signaling CARs,” he said. “[For example,] I want the T cell to recognize this cancer by CAR, but I also want it to do something else—maybe secrete a cytokine, target another immunosuppressive cell, or reverse an exhaustion signal from being suppressive to being activating. That’s our entryway in terms of attacking the more common solid tumor malignancies, which have adapted to evade T cells in the immune system.”
Dr. Davila said many in the field see the value in this work and are also working to mutate CAR signaling domains to improve outcomes with this technology—including research teams at Memorial Sloan Kettering Cancer Center, the University of Pennsylvania, and Fred Hutchinson Cancer Research Center.
“In the next few years, we’re going to see multiple CARs from these groups making it into patients,” he said, noting that the hope is to see the current 30% complete response rate improve to 40% to 50% or beyond with this improved technology.
B-cell malignancies had their first approval; myeloma will likely be next, he said. “That leaves the last big hematologic malignancy: acute myeloid leukemia (AML),” he said. Dr. Davila’s research, and others, are targeting AML with CAR T-cell technology. However, there is a concern that targets are also expressed on hematopoietic stem cells, which could potentially lead to bone marrow failure—a serious toxicity. But the need for therapies in this patient population is high, and clinical trials are underway.
“My hope is that in 5 to 10 years at ASH, we will be focused on talking about CARs for B-cell malignancies, myeloma, and AML,” he concluded.
Dr. Davila is working with Atara Biotherapeutics in developing novel treatments for patients with cancer, autoimmune, and viral diseases. Atara Biotherapeutics is a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases. Atara’s off-the-shelf, allogeneic T cells are bioengineered from donors with healthy immune function and allow for rapid delivery to patients without a requirement for pretreatment.