Reprogramming engineered autologous T cells to overcome resistance in patients with Merkel cell carcinoma.

Engineered TCR T cells targeting MCPyV oncoprotein achieved tumor regression in MCC but faced immune escape due to HLA class I silencing.

• Why it matters: Overcoming resistance to immune checkpoint inhibitors in Merkel cell carcinoma is critical, as most patients develop tumor immune evasion, limiting current therapies.
• What they did: Seven patients received TCR MCC1-engineered T cells after lymphodepletion and HLA-enhancement strategies, with some showing tumor regression and immune activation.
• The result: Modified T cells coexpressing CD8αβ and a CD200R-CD28 switch receptor improved tumor infiltration, HLA expression, and control of HLA-low MCC, offering a strategy to counter immune escape.