ImmunoBody®‐HAGE derived vaccine induces immunity to HAGE and delays the growth and metastasis of HAGE‐expressing tumours in vivo

Nagarajan, D., Pearson, J. ORCID: 0000-0003-1687-5955, Brentville, V., Metheringham, R., Pockley, A.G. ORCID: 0000-0001-9593-6431, Durrant, L. and McArdle, S.E. ORCID: 0000-0001-6929-9782, 2021. ImmunoBody®‐HAGE derived vaccine induces immunity to HAGE and delays the growth and metastasis of HAGE‐expressing tumours in vivo. Immunology and Cell Biology. ISSN 0818-9641

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Abstract

The management of patients with triple-negative breast cancer (TNBC) continues to pose a significant clinical challenge. Less than 30% of women with metastatic TNBC survive 5 years, despite adjuvant chemotherapy and the initial higher rates of clinical response that can be achieved with neoadjuvant chemotherapy. ImmunoBody® is a plasmid DNA designed to encode a human antibody molecule with complementary determining regions (CDRs) engineered to express cytotoxic and helper T cell epitopes derived from the cancer antigen of interest. HAGE is a Cancer Testis Antigen, which is expressed in TNBC. Herein, we have identified a 30-amino-acid-long HAGE-derived sequence containing HLA-A2 and HLA-DR1 restricted epitopes and demonstrated that the use of this sequence as peptide (with CpG/IFA) or incorporated into an ImmunoBody® vaccine can generate specific IFNγ secreting splenocytes in HHDII/DR1 mice. T-cell responses elicited by the ImmunoBody®-HAGE vaccine were superior to peptide immunisation. Moreover, splenocytes from ImmunoBody®-HAGE vaccinated mice stimulated in vitro could recognise HAGE+ tumour cells and the human TNBC cell line MDA-MB-231. More importantly, the growth of implanted B16/HHDII/DR1/HAGE+ cells was significantly delayed by the ImmunoBody®-HAGE vaccine in both prophylactic and experimental metastasis settings. Overall, we demonstrate the potential of HAGE-derived vaccines for treating HAGE-expressing cancers and that such vaccines could be considered as therapeutic options for patients with HAGE+ TNBC after conventional treatment to prevent disease recurrence.

Item Type: Journal article
Publication Title: Immunology and Cell Biology
Creators: Nagarajan, D., Pearson, J., Brentville, V., Metheringham, R., Pockley, A.G., Durrant, L. and McArdle, S.E.
Publisher: Wiley
Date: 9 June 2021
ISSN: 0818-9641
Identifiers:
NumberType
10.1111/imcb.12485DOI
1448219Other
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 28 Jun 2021 09:59
Last Modified: 28 Jun 2021 09:59
URI: http://irep.ntu.ac.uk/id/eprint/43257

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