A detailed analysis of CAR T therapy has identified two kinds of cells, one acting fast, the other over a long period.
Researchers in Texas, USA, describe the CD28.zeta-CAR T cells as “sprinters”, acting quickly and efficiently to kill cancers cells - but with short-lived activity. They compare 4-1BB.zeta-CAR T cells to “marathon runners”.
They have published their findings in Science Advances, saying they hope it will help tailor therapy for hard-to-treat cancers.
The researchers isolated membrane lipid rafts to enable them to biopsy the immunological synapse of the CAR T cells. They found that CD28.zeta-CAR molecules shuttled through the synapse quickly, killing cancer cells within minutes. In contrast, the 4-1BB.zeta-CAR molecules “lingered” in the lipid rafts, multiplying and working together.
Researcher Professor Nabil Ahmed, a haematologist at Baylor College of Medicine, Houston, said: “We need to understand what’s happening at the molecular level so we can engineer CAR T cells to adapt their killing behaviour to target hard-to-treat malignancies, such as solid tumours.”
Fellow researcher Dr Ahmed Gad said: “Observing the distinct pattern of dynamics between single molecules helps us understand the big picture of how these products work. Next, we are studying how to dynamically adapt these CAR T cells at the synapse level to make them more effective.”
Source:
Gad AZ, Morris JS, Godret-Miertschin L, Montalvo MJ, Kerr SS, Berger H, Lee JCH, Saadeldin AM, Abu-Arja MH, Xu S, Vasileiou S, Brock RM, Fousek K, Sheha MF, Srinivasan M, Li Y, Saeedi A, R Levental K, Leen AM, Mamonkin M, Carisey A, Varadarajan N, Hegde M, Joseph SK, Levental I, Mukherjee M, Ahmed N. (2025) “Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.” Science Advances, 10 January 2025, doi: 10.1126/sciadv.adq8114.
Link: https://www.science.org/doi/10.1126/sciadv.adq8114
Disclaimer: The news stories shared on this site are used as a way to inform our members and followers of updates and relevant information happening in Haematology. The BSH does not endorse the content of news items from external sources, and is not in a position to verify the findings, accuracy or the source of any studies mentioned. Any medical or drugs information is provided as an information resource only, and is not to be relied on for any diagnostic or treatment purposes.
News service provided by Englemed News.