Cancer Immunology, Immunotherapy

, Volume 63, Issue 2, pp 101–109 | Cite as

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

  • Mary L. Disis
  • Yushe Dang
  • Andrew L. Coveler
  • Edmond Marzbani
  • Zhong C. Kou
  • Jennifer S. Childs
  • Patricia Fintak
  • Doreen M. Higgins
  • Jessica Reichow
  • James Waisman
  • Lupe G. Salazar
Original Article


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.


HER2 Adoptive T-cell therapy Phase I Clinical trial Vaccine 



This work was supported by Mr. and Mrs. Gavin Herbert, a grant from the Arnold and Mabel Beckman Foundation, Gateway, and NIHUL1TR000423. Most importantly, we acknowledge the invaluable contribution of the patients who volunteered to participate in this study.

Conflict of interest

Mary L. Disis is an inventor on patents held by the University of Washington that pertain to data presented in this manuscript. Zhong C. Kou is the founder of Biomed Immunotech, Inc. which holds proprietary technology on TCR analysis. All other authors do not have any conflicts to disclose.

Supplementary material

262_2013_1489_MOESM1_ESM.pdf (849 kb)
Supplementary material 1 (PDF 849 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Mary L. Disis
    • 1
  • Yushe Dang
    • 1
  • Andrew L. Coveler
    • 1
  • Edmond Marzbani
    • 1
  • Zhong C. Kou
    • 2
  • Jennifer S. Childs
    • 1
  • Patricia Fintak
    • 1
  • Doreen M. Higgins
    • 1
  • Jessica Reichow
    • 1
  • James Waisman
    • 3
  • Lupe G. Salazar
    • 1
  1. 1.Tumor Vaccine Group, Center for Translational Medicine in Women’s HealthUniversity of WashingtonSeattleUSA
  2. 2.BioMed Immunotech, Inc.TampaUSA
  3. 3.City of HopeDuarteUSA

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