HER-2/neu vaccine-primed autologous T-cell infusions for the treatment of advanced stage HER-2/neu expressing cancers

Original Articles
Cancer Immunology Immunotherapy
Disis, M.L., Dang, Y., Coveler, A.L., Marzbani, E., Kou, Z.C., Childs, J.S., Fintak, P., Higgins, D.M., Reichow, J., Waisman, J. and Salazar, L.G.
Description / Abstract: 

This phase I study evaluated the feasibility of expanding HER-2/neu (HER2) vaccine-primed peripheral blood T-cells ex vivo and assessed the safety of T-cell infusions. Eight patients with HER2(+) treatment refractory metastatic cancers were enrolled. T-cells could be expanded to predefined parameters in seven patients (88%). Ninety-two percent of adverse events were grade 1 or 2. Three of seven patients developed infusion-related inflammatory reactions at their disease sites. HER2-specific T-cells significantly increased in vivo compared to pre-infusion levels (p = 0.010) and persisted in 4/6 patients (66%) over 70 days after the first infusion. Partial clinical responses were observed in 43% of patients. Levels of T-regulatory cells in peripheral blood prior to infusion (p < 0.001), the level of HER2-specific T-cells in vivo (p = 0.030), and development of diverse clonal T-cell populations (p < 0.001) were associated with response. The generation of HER2 vaccine-primed autologous T-cells for therapeutic infusion is feasible and well tolerated. This approach provides a foundation for the application of T-cell therapy to additional solid tumor types.

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