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Clin Cancer Res. 2017 Jun 15;23(12):2961-2971. doi: 10.1158/1078-0432.CCR-16-1924. Epub 2016 Dec 13.

Dendritic Cell Vaccination Enhances Immune Responses and Induces Regression of HER2pos DCIS Independent of Route: Results of Randomized Selection Design Trial.

Author information

1
Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
2
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
3
Division of Medical Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
4
Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
5
Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
6
Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Brian.Czerniecki@Moffitt.org.

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 HER2pos patients [42 pure ductal carcinoma in 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 or in vitro sensitization 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 HER2pos 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. Clin Cancer Res; 23(12); 2961-71. ©2016 AACR.

PMID:
27965306
DOI:
10.1158/1078-0432.CCR-16-1924
[Indexed for MEDLINE]
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