Two Fred Hutchinson Cancer Research Center teams have received new funding for in-depth study of the results emerging from ongoing trials of genetically engineered T cell therapies. The studies, led by Drs. Brian Till and Cameron Turtle, will complement Hutch clinical trials of CAR T cell products in certain B cell blood cancers. (CAR stands for “chimeric antigen receptor” and it refers to the T cells’ cancer-targeting technology.)

The awards were made through the Hutch’s Immunotherapy Integrated Research Center, or IIRC, which offers funding to Hutch investigators to advance innovative, collaborative, immunotherapy research.

Till’s new IIRC-funded project complements a recently opened clinical trial of a CAR T cell product aimed at non-Hodgkin lymphomas expressing the CD20 protein. The investigators, including Till and Hutch colleague Dr. Robert Pierce, will carry out a variety of immunological, genetic, and gene-expression studies to understand the reasons for treatment failure in some participants in this trial. These data will be critical for improving the next iterations of this experimental therapy, as well as other kinds of CAR T cell therapies, the research team anticipates.

“The reasons why CAR T cells work in some patients but not in others are unclear in most cases. We hope that these studies will identify what the limiting factors are and point the way toward how to improve future versions of CAR T cell therapy,” said Till, an assistant member of the Hutch’s Clinical Research Division.

Turtle’s newly funded project complements a large ongoing trial of a CAR T cell product to treat leukemias and lymphomas bearing the CD19 protein. The team will identify epigenetic factors that control the proliferation of the genetically engineered cells after they are infused into a patient. The investigators hope that their results will provide insights into the cells’ intrinsic factors that control their activity and could contribute to the therapy’s toxicities or efficacy in eradicating disease. The cross-disciplinary project is a collaboration with the Hutch labs of Drs. Steve Henikoff and Raphael Gottardo.

“Identifying the determinants of in vivo CAR T cell proliferation is key to the development of safe and effective CAR T cell immunotherapy,” said Turtle, an associate member of the Hutch’s Clinical Research Division.

Each award is for $100,000 in direct costs. The projects were funded with philanthropic gifts from the Bezos family following a competitive, external review process that was managed through the IIRC.