title: Delayed-type hypersensitivity response is a predictor of peripheral blood T-cell immunity after HER-2/neu peptide immunization.
abstract: Many groups that immunize cancer patients with cancer vaccines use the generation of a delayed-type hypersensitivity (DTH) response as the primary measure of the ability to immunize a patient to a tumor cell or specific tumor antigen. This study examines whether the development of a tumor antigen-specific DTH response, measured after vaccination with peptide-based vaccines, correlates to in vitro assessment of peripheral blood antigen-specific T-cell responses. The HER-2/neu protein was used as a model tumor antigen. Thirty-two patients who completed a course of immunization with HER-2/neu peptide-based vaccines were analyzed. HER-2/neu peptide-specific DTH responses (n = 93) and peripheral blood T-cell responses (n = 93) were measured 30 days after the final immunization. Size of DTH induration was correlated with HER-2/neu-specific T-cell proliferative responses assessed from peripheral blood lymphocytes isolated concurrently with peptide skin test placement. HER-2/neu peptide-specific DTH responses > or =10 mm2 correlated significantly to a measurable peptide-specific peripheral blood T-cell response defined as stimulation index >2.0 (P = 0.0006). However, antigen-specific DTH responses with magnitudes between 5 and 9 mm2 were not significantly associated with the development of systemic immunity. DTH responses between 5 and 9 mm2 carried an odds ratio of 1.3 (P = 0.61) in predicting a measurable systemic tumor antigen response. The findings presented here demonstrate that tumor antigen-specific DTH responses > or =10 mm2 correlate with measurable in vitro antigen-specific lymphocytic proliferation and are, in this model system, a reflection of systemic immunization.
authors.affiliation: Division of Oncology, University of Washington, Seattle 98195, USA. ndisis@u.washington.edu
authors.forename: M L
authors.initials: ML
authors.lastname: Disis
authors.forename: K
authors.initials: K
authors.lastname: Schiffman
authors.forename: T A
authors.initials: TA
authors.lastname: Gooley
authors.forename: D G
authors.initials: DG
authors.lastname: McNeel
authors.forename: K
authors.initials: K
authors.lastname: Rinn
authors.forename: K L
authors.initials: KL
authors.lastname: Knutson
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology / Q000517:prevention & control; D019496:Cancer Vaccines / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000517:prevention & control; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular; D007114:Immunization; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control; D008213:Lymphocyte Activation; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology / Q000517:prevention & control; D010446:Peptide Fragments / Q000276:immunology; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D012882:Skin Tests; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases