title: Dendritic Cell Vaccination Enhances Immune Responses and Induces Regression of HER2posDCIS Independent of Route: Results of Randomized Selection Design Trial.
abstract: Purpose:Vaccination with HER2 peptide-pulsed DC1s stimulates a HER2-specific T-cell response. This randomized trial aimed to establish safety and evaluate immune and clinical responses to vaccination via intralesional (IL), intranodal (IN), or both intralesional and intranodal (ILN) injection.Experimental Design:Fifty-four HER2pospatients [42 pure ductal carcinomain situ(DCIS), 12 early invasive breast cancer (IBC)] were enrolled in a neoadjuvant HER2 peptide-pulsed DC1 vaccine trial. Patients were randomized to IL (n= 19), IN (n= 19), or ILN (n= 16) injection. Immune responses were measured in peripheral blood and sentinel lymph nodes by ELISPOT orin vitrosensitization assay. Pathologic response was assessed in resected surgical specimens.Results:Vaccination by all injection routes was well tolerated. There was no significant difference in immune response rates by vaccination route (IL 84.2% vs. IN 89.5% vs. ILN 66.7%;P= 0.30). The pathologic complete response (pCR) rate was higher in DCIS patients compared with IBC patients (28.6% vs. 8.3%). DCIS patients who achieved pCR (n= 12) and who did not achieve pCR (n= 30) had similar peripheral blood anti-HER2 immune responses. All patients who achieved pCR had an anti-HER2 CD4 immune response in the sentinel lymph node, and the quantified response was higher by response repertoire (P= 0.03) and cumulative response (P= 0.04).Conclusions:Anti-HER2 DC1 vaccination is a safe and immunogenic treatment to induce tumor-specific T-cell responses in HER2pospatients; immune and clinical responses were similar independent of vaccination route. The immune response in the sentinel lymph nodes, rather than in the peripheral blood, may serve as an endpoint more reflective of antitumor activity.Clin Cancer Res; 23(12); 2961-71. ©2016 AACR.
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Lea
authors.initials: L
authors.lastname: Lowenfeld
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mick
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Jashodeep
authors.initials: J
authors.lastname: Datta
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fitzpatrick
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Carla S
authors.initials: CS
authors.lastname: Fisher
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Fox
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Angela
authors.initials: A
authors.lastname: DeMichele
authors.affiliation: Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Zhang
authors.affiliation: Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Weinstein
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Roses
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Brian.Czerniecki@Moffitt.org.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Czerniecki
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology; D000071036:Sentinel Lymph Node / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human