The long-held hope that vaccination strategies might be effective against cancer has motivated numerous attempts over the past century to put the idea to test in the clinic. Although the generally disappointing results have cast a long shadow over the field, advances in cancer immunology growing on the remarkable insights from basic immunology provide a strong foundation and powerful new tools to guide current attempts to fashion effective cancer vaccines. This review covers the scientific basis and rationale for cancer vaccines, the challenges involved in assembling the many ingredients going into the construction of cancer vaccines, and the daunting obstacles confronting academic investigators wanting to transfer their discoveries into the clinical arena. The Cancer Vaccine Collaborative (CVC), a partnership between the Cancer Research Institute and the Ludwig Institute for Cancer Research, represents a new academic model for developing, coordinating, conducting, and monitoring cancer vaccine trial. NY-ESO-1, a prototype cancer-testis (CT) antigen having strong spontaneous humoral and cellular immunogenicity, has been chosen as the initial CVC vaccine target, and the current status of NY-ESO-1 vaccine trials carried at the multiple CVC sites around the world is discussed.

This article was published in Cancer Immunity, a Cancer Research Institute journal that ceased publication in 2013 and is now provided online in association with Cancer Immunology Research.