Development of modified vaccinia Ankara-5T4 as specific immunotherapy for advanced human cancer

Background: The tumor-associated antigen 5T4 is expressed on a high percentage of human carcinomas and has limited expression in normal tissues. A recombinant pox virus vector expressing this antigen, modified vaccinia Ankara (MVA)-5T4, has been tested as a cancer vaccine. Objective: Treatment with MVA-5T4 has been studied both as a single agent and in combination with standard chemo-, biologic- or targeted-therapies in patients with advanced colorectal cancer, renal cell carcinoma (RCC) or hormone-refractory prostate cancer. Methods: This review summarizes data from clinical studies with MVA-5T4 reported in published manuscripts, meeting abstracts or posted on websites relevant to clinical trials or MVA-5T4. Results/conclusion: Vaccination with MVA-5T4 is well tolerated and elicits 5T4-specific humoral and/or cellular responses in most of the treated patients. Retrospective analyses of Phase II studies have suggested a positive association between immune responses to 5T4 and favorable clinical outcomes. A continuing Phase III, double-blind, placebo-controlled trial seeks to confirm a positive association between vaccination with MVA-5T4 and survival in patients with advanced RCC.

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