Anti-CD3 Fab fragments enhance tumor killing by human γδ T cells independent of Nck recruitment to the γδ T cell antigen receptor
Juraske C, Wipa P, Morath A, Hidalgo JV, Hartl FA, Raute K, Oberg HH, Wesch D, Fisch P, Minguet S, Pongcharoen S, Schamel WW.
In this BIOSS publication we used our knowledge on the functioning of the γδ T cell antigen receptor (γδ TCR), to enhance tumour killing by γδ T cells. We demonstrate that Fab fragments of the anti-CD3ε antibody UCHT1 enhanced tumor killing by expanded human γδ T cells derived of the peripheral blood of healthy donors. The Fab fragments induced Nck recruitment to the γδ TCR, suggesting that they stabilized the γδ TCR in an active CD3ε conformation. However, blocking the Nck-CD3ε interaction in γδ T cells using the small molecule inhibitor AX-024 neither reduced the γδ T cells' natural nor the Fab-enhanced tumor killing activity. Likewise, Nck recruitment to CD3ε was not required for intracellular signaling, CD69 and CD25 up-regulation, or cytokine secretion by γδ T cells. Thus, the Nck-CD3ε interaction seems to be dispensable fort he activation of γδ T cells. In conclusion, this publication might be another step towards cancer immunotherapy using γδ T cells.
