We have developed several cancer vaccine strategies and translated them from mice to humans. We used “epitope enhancement” to modify an epitope of the TARP prostate cancer antigen to increase affinity for HLA-A2 and immunogenicity in HLA-A2-transgenic mice. This and another high affinity TARP epitope elicited human T cells killing human tumor cells. We translated these into a vaccine trial in stage D0 prostate cancer, in which patients after primary disease treatment have rising PSA. Patients received TARP peptides either in montanide or pulsed onto autologous DCs. No difference was seen between arms. 72% of vaccinees at 24 wks and 74% at 48 wks had a decreased PSA velocity (p= 0.0004), a validated measure of tumor growth. 77% of vaccinees made a specific IFNγ ELISpot response, but there was no correlation with clinical effect, suggesting that the quality of the T cells is critical. Accordingly, a phase II randomized placebo-controlled clinical trial is being opened. We also developed an adenovirus vaccine expressing the extracellular & transmembrane domains of HER2, which cured almost all mice with large (up to 2 cm) established tumors and lung metastases. The protection in mice is purely antibody-dependent. We translated this to a clinical trial with autologous DCs transduced with an adenovirus expressing human HER2 domains. The first part is a dose-escalation in patients with any type of cancer expressing 1+ to 3+ HER2 by IHC who are naïve to HER2-targeted therapies. In 1 of 2 patients so far at the 2nd dose level for which we have data, we have an indication of a partial response. Thus, translation of cancer vaccine strategies from mice to humans is beginning to show promising results.
Citation Format: Jay A. Berzofsky, Masaki Terabe, Lauren V. Wood. Translation of cancer vaccine strategies from mice to clinical trials. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B26.