Polyomavirus-driven Merkel cell carcinoma: Prospects for therapeutic vaccine development

Mol Carcinog. 2020 Jul;59(7):807-821. doi: 10.1002/mc.23190. Epub 2020 Mar 27.


Great strides have been made in cancer immunotherapy including the breakthrough successes of anti-PD-(L)1 checkpoint inhibitors. In Merkel cell carcinoma (MCC), a rare and aggressive skin cancer, PD-(L)1 blockade is highly effective. Yet, ~50% of patients either do not respond to therapy or develop PD-(L)1 refractory disease and, thus, do not experience long-term benefit. For these patients, additional or combination therapies are needed to augment immune responses that target and eliminate cancer cells. Therapeutic vaccines targeting tumor-associated antigens, mutated self-antigens, or immunogenic viral oncoproteins are currently being developed to augment T-cell responses. Approximately 80% of MCC cases in the United States are driven by the ongoing expression of viral T-antigen (T-Ag) oncoproteins from genomically integrated Merkel cell polyomavirus (MCPyV). Since T-Ag elicits specific B- and T-cell immune responses in most persons with virus-positive MCC (VP-MCC), and ongoing T-Ag expression is required to drive VP-MCC cell proliferation, therapeutic vaccination with T-Ag is a rational potential component of immunotherapy. Failure of the endogenous T-cell response to clear VP-MCC (allowing clinically evident tumors to arise) implies that therapeutic vaccination will need to be potent anśd synergize with other mechanisms to enhance T-cell activity against tumor cells. Here, we review the relevant underlying biology of VP-MCC, potentially applicable therapeutic vaccine platforms, and antigen delivery formats. We also describe early successes in the field of therapeutic cancer vaccines and address several clinical scenarios in which VP-MCC patients could potentially benefit from a therapeutic vaccine.

Keywords: MCPyV; Merkel cell carcinoma; cancer therapeutic vaccine; immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Viral, Tumor / immunology
  • Carcinoma, Merkel Cell / immunology*
  • Carcinoma, Merkel Cell / therapy
  • Carcinoma, Merkel Cell / virology
  • Humans
  • Immunotherapy / methods
  • Merkel cell polyomavirus / immunology*
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / therapy
  • Skin Neoplasms / virology
  • T-Lymphocytes / immunology
  • Vaccines / immunology*


  • Antigens, Viral, Tumor
  • Vaccines