title: HER-2/neu vaccine-primed autologous T-cell infusions for the treatment of advanced stage HER-2/neu expressing cancers.
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.
authors.affiliation: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, 850 Republican Street, Box 358050, Seattle, WA, 98195-8050, USA, ndisis@uw.edu.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Disis
authors.forename: Yushe
authors.initials: Y
authors.lastname: Dang
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Coveler
authors.forename: Edmond
authors.initials: E
authors.lastname: Marzbani
authors.forename: Zhong C
authors.initials: ZC
authors.lastname: Kou
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Childs
authors.forename: Patricia
authors.initials: P
authors.lastname: Fintak
authors.forename: Doreen M
authors.initials: DM
authors.lastname: Higgins
authors.forename: Jessica
authors.initials: J
authors.lastname: Reichow
authors.forename: James
authors.initials: J
authors.lastname: Waisman
authors.forename: Lupe G
authors.initials: LG
authors.lastname: Salazar
mesh_terms: D019264:Adoptive Transfer / Q000009:adverse effects / Q000379:methods*; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases