5T4-modified vaccinia Ankara: progress in tumor-associated antigen-based immunotherapy

Importance of the field: The expression and biology of the tumor-associated antigen (TAA) 5T4 suggest it is an effective target for cancer immunotherapy. Areas covered in this review: Development of a vaccine comprising highly attenuated modified vaccinia Ankara virus encoding 5T4 (MVA-5T4, a.k.a. TroVax(R)). What the reader will gain: Preclinical studies demonstrated that MVA-5T4 is safe and effective in prophylactic and active treatment of syngeneic murine tumor models. Over 700 doses of MVA-5T4 have been administered to over 200 patients to date. Results from clinical trials on metastatic colorectal, metastatic renal and hormone-refractory prostate cancer patients demonstrate that MVA-5T4 is safe and immunogenic as a monotherapy and in combination with standard-of-care therapies. MVA-5T4 induced potent and sustained immune responses in approximately 95% of tested patients. Post hoc analyses have noted a correlation between anti-5T4 immune responses and indicators of clinical benefit. A Phase III randomized, placebo controlled study, which investigated MVA-5T4 added to first line standard of care to evaluate whether vaccination prolonged survival of patients with metastatic clear cell renal cell cancer did not meet the primary endpoint (overall survival). Take home message: With its minimal side effects and ability to produce immune responses MVA-5T4 is a promising addition to the cancer therapy arsenal.