Merkel cell polyomavirus Large T antigen (MCPyV LT) (MCPyV LT)

The Merkel cell polyomavirus Large T antigen (MCPyV LT) is a multifunctional viral oncoprotein that plays a central role in the pathogenesis of Merkel cell carcinoma (MCC) [1, 2]. In tumor cells, the LT gene is typically integrated into the host genome and carries specific mutations that result in a truncated protein; this truncation preserves the N-terminal CR1 and DnaJ domains and the Retinoblastoma (RB) protein-binding motif while eliminating the C-terminal helicase domain [3, 4]. The preservation of the RB-binding motif allows the truncated LT to sequester the RB1 tumor suppressor, thereby driving uncontrolled cell cycle progression and tumor growth [2, 3]. Because MCPyV LT is a non-self viral protein expressed exclusively in tumor cells, it serves as a potent neoantigen for the immune system [5]. Therapeutic strategies targeting this antigen include immune checkpoint inhibitors like avelumab, which enhance the endogenous T-cell response, as well as experimental approaches such as TCR-engineered T-cell therapies and therapeutic vaccines designed to elicit specific cytotoxic activity against LT-positive cells [5, 6]. Monitoring the presence of LT antigen and the titers of antibodies directed against it is clinically useful for diagnosing MCC and tracking treatment response [4].

Other names

MCPyV Large T-antigenLT antigenMerkel cell polyomavirus Large T-proteinTruncated Large T antigen

Immune checkpoint inhibition to enhance T-cell mediated destruction of LT-expressing tumor cells; Adoptive T-cell transfer of TCR-engineered T cells specific for LT epitopes; Induction of antigen-specific cellular immunity via therapeutic vaccination [4, 5, 6].