Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients
Keith L. Knutson, … , Kathy Schiffman, Mary L. Disis
Keith L. Knutson, … , Kathy Schiffman, Mary L. Disis
Published February 15, 2001
Citation Information: J Clin Invest. 2001;107(4):477-484. https://doi.org/10.1172/JCI11752.
View: Text | PDF
Article

Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients

Abstract

CD4 T-cell help is required during the generation and maintenance of effective antitumor CD8 T cell–mediated immunity. The goal of this study was to determine whether HER-2/neu–specific CD8 T-cell immunity could be elicited using HER-2/neu–derived MHC class II “helper” peptides, which contain encompassed HLA-A2–binding motifs. Nineteen HLA-A2 patients with HER-2/neu–overexpressing cancers received a vaccine preparation consisting of putative HER-2/neu helper peptides p369–384, p688–703, and p971–984. Contained within these sequences are the HLA-A2–binding motifs p369–377, p689–697, and p971–979. After vaccination, the mean peptide-specific T-cell precursor frequency to the HLA-A2 peptides increased in the majority of patients. In addition, the peptide-specific T cells were able to lyse tumors. The responses were long-lived and detectable for more than 1 year after the final vaccination in select patients. These results demonstrate that HER-2/neu MHC class II epitopes containing encompassed MHC class I epitopes are able to induce long-lasting HER-2–specific IFN-γ–producing CD8 T cells.

Authors

Keith L. Knutson, Kathy Schiffman, Mary L. Disis

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
The majority of patients could be immunized to HER-2/neu. Data are shown...
The majority of patients could be immunized to HER-2/neu. Data are shown as the percentage of the population before immunization and after immunization that had a positive proliferation response (SI > 2) to each of the peptides in the vaccine, p369–384 (light gray bar), p688–703 (gray bar), p971–984 (filled bar), as well as to the HER-2 protein domains, ECD (open bar) and ICD (dark gray bar). The mean (range) preimmunization SI of patients considered as having a positive response to p369–384 was 2.4 (one patient only), to p688–703 was 2.5 (2.4–2.5), to p971–984 was 2.5 (one patient only), to ECD (no patients), and to ICD was 2.2 (one patient only). The mean (range) postimmunization SI of patients considered as having a positive response to p369–384 was 7.5 (2.9–35.6), to p688–703 was 3.5 (2.1–6.4), to p971–984 was 6.2 (2.4–26.1), to ECD was 3.3 (2.5–5.1), and to ICD was 6.2 (2.7–18).