Abstract
Abstract
Introduction:
We have developed an autologous HER2-pulsed dendritic cell (DC) vaccine that induces robust T-cell responses in early breast cancer. We have also previously demonstrated anti-HER2 Th1 responses to select class II peptides are preferentially lost early in HER2pos breast tumorigenesis. We aimed to compare peptide-specific Th1 responses between pathologic complete (pCR) and incomplete responders (<pCR) following HER2-pulsed DC vaccination.
Methods:
Patients with HER2pos DCIS (n = 37) or stage I invasive breast cancer (IBC) (n = 10) received neoadjuvant HER2-pulsed DC vaccine prior to surgery. Specimens were examined for residual disease on pathology. CD4 Th1 responses to 6 HER2 Class II peptides (p42-56, p98-114, p328-345, p776-790, p927-941, p1166-1180) were measured using IFN-γ production by ELISPOT. Th1 response metrics were: (1) anti-HER2 responsivity, (2) response repertoire (i.e. no. of reactive peptides), and (3) cumulative response. Th1 responses post-vaccination were compared between pCR (n = 11) and <pCR (n = 36).
Results:
Forty-three of 47 (91.5%) vaccinated subjects mounted CD4 Th1 responses post-vaccination. Eleven of 47 (23.4%) achieved pCR; no significant difference in pCR rates were observed between IBC and DCIS patients (10% vs 27.0%; p = 0.41). pCR and <pCR patients did not differ by anti-HER2 responsivity (90.9% pCR vs 91.7% 0.05). We previously reported a significant loss of anti-HER2 Th1 responses to p42-56 and p927-941 very early in breast tumorigenesis (i.e. from healthy donors to DCIS ultimately to IBC). In this study, compared to <pCR, pCR patients demonstrated a significantly higher anti-HER2 responsivity (72.7% pCR vs 33.0% <pCR, p = 0.04) and response magnitude (354 vs 110; p = 0.04) to vaccination with p42-56; in addition, there was a trend toward higher response magnitude (318 pCR vs 168 <pCR, p = 0.06) to p927-941 vaccination. No differences were observed in the remaining four peptide responses between pCR and <pCR patients.
Conclusion:
HER2-pulsed DC vaccination induces pathologic responses in early breast cancer patients, supporting further clinical development. The key immunogenic HER2 class II peptides that appear to drive pCR following DC vaccination are incidentally lost very early in tumorigenesis, suggesting that immune restoration targeting these select peptides may enable control of early breast cancer.
Citation Format: Megan E. Fracol, Jashodeep Datta, Shuwen Xu, Lea Lowenfeld, Elizabeth Fitzpatrick, Carolyn Mies, Paul J.L. Zhang, Robert E. Roses, Carla Fisher, Brian J. Czerniecki. HER2 peptide-specific immunogenicity correlates with pathologic response following HER2-pulsed dendritic cell vaccination for early breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2489. doi:10.1158/1538-7445.AM2015-2489
