A battle of rafts: How molecular dynamics in CAR T cells explain their cancer-killing behavior

A new study in Science Advances reveals the molecular dynamics that govern the effectiveness of anticancer immunotherapies. Researchers at Baylor College of Medicine, Texas Children's Cancer Center, the Center for Cell and Gene Therapy, and Houston Methodist studied how the interface between CAR T cells and cancer cells, the immune synapse, affects the potency and duration of CAR T cell cancer-killing activity. 

Led by (pictured, L-R) senior author Dr. Nabil Ahmed and first author Dr. Ahmed Gad, the team biopsied the CAR T cell immunological synapses by isolating membrane lipid rafts, where most molecular interactions between cells take place. They found that the killing dynamics are mirrored in how CAR molecules are shuttled through the synapse, with CD28.ζ-CAR T cells acting quickly but briefly, and 4-1BB.ζ-CAR T cells providing sustained killing over time.

This study paves the way towards the intelligent design of CAR T cells capable of targeting hard-to-treat malignancies.

A huge thank you to the following foundations and agencies for enabling this work: National Institutes of Health (NIH), National Cancer Institute, Cancer Prevention and Research Institute of Texas (CPRIT), St. Baldrick's Foundation, Stand Up To Cancer, Triumph Over Kid Cancer Foundation and The Faris Foundation.

Read the full article on BCM.edu

View the publication on Science.org