Engineered T Cells Devised to Target Merkel Cell Carcinoma Cells
Posted: Tuesday, July 24, 2018
The results of genetic engineering work targeting Merkel cell carcinoma was reported in Clinical Cancer Research, describing how tumors in a mouse model regressed upon treatment with T-cell receptors.
“Although recent findings suggest that approximately half of Merkel cell carcinoma patients benefit from PD-1 pathway blockade, additional patients may benefit if their endogenous T-cell response can be augmented by infusion of transgenic MCV-specific T cells such as those described here,” noted Prof. Dr. Thomas Blankenstein, of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany, and colleagues.
The research team started with the premise that most cases of Merkel cell carcinoma are caused by the Merkel cell polyomavirus (MCV). For Merkel cell tumors to grow, the MCVs need MCV-encoded T antigens (Tags). T-cell therapy targeting the destruction of Tags, then, would logically disrupt Merkel cell carcinoma.
The researchers sought to isolate T-cell receptors that were Tag-specific. They genetically engineered human lymphocytes to express such T-cell receptors. In successful experiments, “we showed [the] cytotoxic potential of T cells engineered to express these [T-cell receptors] in vitro and demonstrated regression of established tumors in a mouse model upon [T-cell receptor] gene therapy,” wrote Dr. Blankenstein and colleagues.
