David Barrett Laboratory

Led by David M. Barrett, MD, PhD, researchers in the Barrett Laboratory are evaluating innovative immunotherapies, such as of Chimeric Antigen Receptor (CAR) T cells, to treat children with hematologic cancers and pediatric tumors. The long-term goal of the research conducted in this laboratory is to develop and clinically evaluate new immunotherapies for pediatric cancers and tumors that are more effective, less toxic and produce fewer side effects than existing cancer treatments.

Ongoing studies in the Barrett Laboratory are investigating the use of CAR T cells redirected against GD2 (an antigen that is over expressed on neuroblastoma tumor cells) as an immunotherapy to treat refractory and relapsed pediatric neuroblastomas. Unlike most other CAR T cells, GD2-redirected CART cells (CART-GD2) were genetically engineered to have short circulating half-lives to protect normal brain tissue from immunoinflammatory responses that may occur during CART treatment.

Researchers in the Barrett Laboratory are currently involved in a Phase I clinical trial to evaluate the effectiveness of CART-GD2 as a treatment for children with relapsed and refractory neuroblastoma.

Other studies in the Barrett Laboratory are focused on elucidating the underlying molecular mechanisms that contribute to development of cytokine release syndrome (CRS). CRS has been observed in some children with acute lymphoblastic leukemia (ALL) who are treated with CART immunotherapy. Clinical studies have revealed that that administration of tocilizumab — an anti-IL6 receptor monoclonal antibody that interferes with secretion of the cytokine IL6 — can be an effective treatment for pediatric patients who develop CRS after CART.

Researchers in the Barrett Laboratory are trying to gain a better understanding of the role of IL6 in CRS and to identify genetic markers that may help to identify children who may be at high risk of developing CRS during CART immunotherapy.

In addition, researchers are looking at the immune function of children with newly diagnosed cancers to gain clues into better ways to predict, prevent and treat cancers differently in the future.

Future studies in the Barrett Laboratory will continue to focus on clinically evaluating new immunotherapies that can be safely and effectively employed to treat pediatric tumors and other malignancies.