Dendritic Cell Vaccination Enhances Immune Responses and Induces Regression of HER2 pos DCIS Independent of Route: Results of Randomized Selection Design Trial

• Published in: Clinical cancer research 2017-06, Vol.23 (12), p.2961
• Main Authors: Lowenfeld, Lea, Mick, Rosemarie, Datta, Jashodeep, Xu, Shuwen, Fitzpatrick, Elizabeth, Fisher, Carla S, Fox, Kevin R, DeMichele, Angela, Zhang, Paul J, Weinstein, Susan P, Roses, Robert E, Czerniecki, Brian J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Breast Neoplasms - drug therapy; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Dendritic Cells - immunology; Dendritic Cells - transplantation; Female; Humans; Immunity, Cellular - drug effects; Immunity, Cellular - immunology; Middle Aged; Neoadjuvant Therapy; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - immunology; Sentinel Lymph Node - drug effects; Sentinel Lymph Node - immunology; T-Lymphocytes - immunology
• ISSN: 1078-0432
• DOI: 10.1158/1078-0432.CCR-16-1924

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. Fifty-four HER2 patients [42 pure ductal carcinoma (DCIS), 12 early invasive breast cancer (IBC)] were enrolled in a neoadjuvant HER2 peptide-pulsed DC1 vaccine trial. Patients were randomized to IL ( = 19), IN ( = 19), or ILN ( = 16) injection. Immune responses were measured in peripheral blood and sentinel lymph nodes by ELISPOT or sensitization assay. Pathologic response was assessed in resected surgical specimens. 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%; = 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 ( = 12) and who did not achieve pCR ( = 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 ( = 0.03) and cumulative response ( = 0.04). Anti-HER2 DC1 vaccination is a safe and immunogenic treatment to induce tumor-specific T-cell responses in HER2 patients; 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. .