CAR-T cells can transfer antitumour immunity to other T cells by exchanging surface proteins

Novel research in cells and mice models has provided insight into the mechanisms that regulate trogocytosis, a process during which immune cells can exchange membrane-bound proteins. The study showed that chimeric antigen receptor cells (so-called CAR-T cells) could transfer tumour antigen-specific receptors to recipient T cells, and in doing so equipped the latter cells with tumour-targeting abilities.

Stefano Barbera and colleagues from Uppsala University, Sweden, also demonstrated that the transmembrane domain of surface proteins determined whether trogocytosis would occur. These findings could inform future T cell-based immunotherapies.

While prior research has shown that trogocytosis can occur between different types of immune cells, it has been unclear why cells can only exchange specific sets of proteins using this process. Some studies have suggested that only proteins with corresponding binding partners on recipient cells can be transferred.

The Uppsala team examined molecule exchange between cultured T cells and found that physical contact was necessary for trogocytosis to occur. The researchers also determined that CAR-T cells could transfer CARs and tumour antigen-specific T cell receptors (TCRs) to recipient immune cells both in vitro and in mouse models of cancer.

Prior exposure to antigen-expressing tumour cells activated donor CAR-T cells and increased trogocytosis efficiency. Furthermore, the researchers found that mouse and human T cells that received tumour-specific CARs and TCRs became activated and acquired tumour-killing abilities. This indicated that CAR-T cells could transfer antitumor immunity to recipients.

The authors then established that T cells could transfer proteins that did not have binding partners on recipient cells. Instead, the transmembrane domains (TM) of proteins modulated the rate of trogocytosis by influencing their localisation at the membrane.

Additionally, the team demonstrated that increasing the flexibility of the TM domains upregulated the transfer of CAR molecules, which could improve the design of future CAR-T cell therapies.

For further reading please visit: 10.1126/sciimmunol.ado2054