Publication Date
6-1-2023
Journal
Cancer Prevention Research
Abstract
UNLABELLED: NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in CTL responses between groups and between pre-vaccination and 1-month post-operation were analyzed using a two-sample t test or Wilcoxon rank sum test. The incidence and severity of adverse events were compared between groups. Overall, 45 patients were registered; 20 patients were HLA-A2 negative, 7 declined participation, 1 withdrew, and 4 failed screening for other reasons. The remaining 13 were randomized to NeuVax (n = 9) or GM-CSF alone (n = 4). Vaccination was well-tolerated with similar treatment-related toxicity between groups with the majority (>89%) of adverse events being grade 1. The percentage of NPS-specific CTLs increased in both arms between baseline (pre-vaccination) and 1-month post-operation. The increase was numerically greater in the NPS+GM-CSF arm, but the difference was not statistically significant. NPS+GM-CSF is safe and well-tolerated when given preoperatively to patients with DCIS. In patients with HLA-A2-positive DCIS, two inoculations with NPS+GM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response 1-month postsurgery.
PREVENTION RELEVANCE: This trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence.
Keywords
Humans, Female, Granulocyte-Macrophage Colony-Stimulating Factor, Carcinoma, Intraductal, Noninfiltrating, HLA-A2 Antigen, Neoplasm Recurrence, Local, Peptide Fragments, Vaccines, Subunit, Cancer Vaccines
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Community Health and Preventive Medicine Commons, Medical Sciences Commons, Obstetrics and Gynecology Commons, Oncology Commons, Women's Health Commons
Comments
Supplementary Materials
PMID: 37259799