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. 2017 May 11;8(7):1255-1262.
doi: 10.7150/jca.16450. eCollection 2017.

Evaluation of Attenuated Tumor Antigens and the Implications for Peptide-Based Cancer Vaccine Development

J S Berry  1 , T J Vreeland  2 , D F Hale  1 , D O Jackson  3 , A F Trappey  3 , J M Greene  3 , M O Hardin  4 , G S Herbert  3 , G T Clifton  5 , G E Peoples  6
Affiliations

Evaluation of Attenuated Tumor Antigens and the Implications for Peptide-Based Cancer Vaccine Development

J S Berry et al. J Cancer. .

Abstract

Introduction: Peptide vaccines offer anti-tumor efficacy with very low toxicity. However, repeat stimulation with an immunogenic peptide leads to activation induced cell death (AICD), decreasing efficacy. We engineered variants of an immunogenic peptide (E39) and tested their ability to induce a robust, sustainable immune response.

Methods: Multiple variants of E39 were created by exchanging 1 or 2 amino acids. We tested the PBMC proliferation, cytokine production and cytolytic activity induced by each variant peptide.

Results: Repeated stimulation with E39 likely led to in vitro AICD, while stimulation with E39' led to T-cell proliferation with less evidence of AICD, modest cytokine production and high CTL activity.

Conclusions: E39' appears to be the optimal variant of E39 for inducing effective long-term immunity.

Keywords: E39; E39'.; Folate binding protein; J65; folate receptor alpha.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
HLA-A2 stabilization of E39-derived attenuated epitopes
Figure 2
Figure 2
PBMC proliferation after stimulation with E39 or E39 derived epitopes; Donor #1.
Figure 3
Figure 3
PBMC proliferation after stimulation with E39 or E39 derived epitopes; Donor #2.
Figure 4
Figure 4
Interleukin 2 (IL-2) levels produced by PBMCs after third priming with E39' E39, and J77.
Figure 5
Figure 5
IFN-γ levels in PBMCs after three weekly stimulations with E39' or E39, followed by a fourth re-stimulation with either E39', E39, or J77.
Figure 6
Figure 6
% specific lysis of CTLs after three weekly E39' or E39 priming doses at different concentrations (0, 5 or 25µg/ml) followed by a single E39', E39, or J77 boosting.
Figure 7
Figure 7
Proposed mechanism of improved T cell response after repeated stimulation with attenuated peptide (E39') and parent peptide (E39).
Figure 8
Figure 8
Phase I/2a trial design in breast and ovarian cancer (NCT02019524)16
See this image and copyright information in PMC

References

    1. Peoples GE, Goedegebuure PS, Andrews JV. et al. HLA-A2 presents shared tumor-associated antigens derived from endogenous proteins in ovarian cancer. J Immunol. 1993;151(10):5481–5491. - PubMed
    1. Yoshino I, Goedegebuure PS, Peoples GE. et al. HER2/neu-derived peptides are shared antigens among human non-small cell lung cancer and ovarian cancer. Cancer Res. 1994;54(13):3387–3390. - PubMed
    1. Li PY, Del Vecchio S, Fonti R. et al. Local concentration of folate binding protein GP38 in sections of human ovarian carcinoma by in vitro quantitative autoradiography. J Nucl Med. 1996;37(4):665–672. - PubMed
    1. Peoples GE, Anderson BW, Lee TV. et al. Vaccine implications of folate binding protein, a novel cytotoxic T lymphocyte-recognized antigen system in epithelial cancers. Clin Cancer Res. 1999;5(12):4214–4223. - PubMed
    1. Peoples GE, Anderson BW, Fisk B. et al. Ovarian cancer-associated lymphocyte recognition of folate binding protein peptides. Ann Surg Oncol. 1998;5(8):743–750. - PubMed