The primary objective of this study was to enhance the antitumor efficacy of a model cancer vaccine through co-delivery of pentaerythritol lipid A (PELA), an immunological adjuvant, and a model tumor antigen, ovalbumin (OVA), separately loaded into polyanhydride particles (PA). In vitro experiments showed that encapsulation of PELA into PA (PA-PELA) significantly enhanced its stimulatory capacity on dendritic cells as evidenced by increased levels of the cell surface costimulatory molecules, CD80/CD86. In vivo experiments showed that PA-PELA, in combination with OVA-loaded PA (PA-OVA), significantly expanded the OVA-specific CD8+ T lymphocyte population compared to PA-OVA alone. Furthermore, serum OVA-specific antibody titers of mice vaccinated with PA-OVA/PA-PELA displayed a significantly stronger shift toward a Th1-biased immune response compared to PA-OVA alone, as evidenced by the substantially higher IgG2C:IgG1 ratios achieved by the former. Analysis of E.G7-OVA tumor growth curves showed that mice vaccinated with PA-OVA/PA-PELA had the slowest average tumor growth rate.