PMID- 34105800 OWN - NLM STAT- MEDLINE DCOM- 20211025 LR - 20220531 IS - 1440-1711 (Electronic) IS - 0818-9641 (Linking) VI - 99 IP - 9 DP - 2021 Oct TI - Helicase antigen (HAGE)-derived vaccines induce immunity to HAGE and ImmunoBody(R)-HAGE DNA vaccine delays the growth and metastasis of HAGE-expressing tumors in vivo. PG - 972-989 LID - 10.1111/imcb.12485 [doi] AB - 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 complementarity-determining regions engineered to express cytotoxic and helper T-cell epitopes derived from the cancer antigen of interest. The helicase antigen (HAGE) is a cancer testis antigen, which is expressed in TNBC. Herein, we have identified a 30-amino-acid-long HAGE-derived sequence containing human leukocyte antigen (HLA)-A2- and HLA-DR1-restricted epitopes and demonstrated that the use of this sequence as a peptide (with CpG/incomplete Freund's adjuvant) or incorporated into an ImmunoBody vaccine can generate specific interferon-gamma-secreting splenocytes in HHDII(+) DR1(+) mice. T-cell responses elicited by the ImmunoBody-HAGE vaccine were superior to peptide immunization. Moreover, splenocytes from ImmunoBody-HAGE-vaccinated mice stimulated in vitro could recognize HAGE(+) tumor cells and the human TNBC cell line MDA-MB-231. More importantly, the growth of implanted HHDII(+) DR1(+) HAGE(+) Luc(+) B16 cells. CI - (c) 2021 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. FAU - Nagarajan, Divya AU - Nagarajan D AD - Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. AD - John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK. AD - Centre for Health, Ageing and Understanding Disease, School of Science and Technology, Nottingham Trent University, Nottingham, UK. FAU - Pearson, Joshua AU - Pearson J AD - John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK. AD - Centre for Health, Ageing and Understanding Disease, School of Science and Technology, Nottingham Trent University, Nottingham, UK. FAU - Brentville, Victoria AU - Brentville V AD - Scancell Ltd, Biodiscovery Institute, University of Nottingham, University Park, Nottingham, UK. FAU - Metheringham, Rachael AU - Metheringham R AD - Scancell Ltd, Biodiscovery Institute, University of Nottingham, University Park, Nottingham, UK. FAU - Pockley, A Graham AU - Pockley AG AD - John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK. AD - Centre for Health, Ageing and Understanding Disease, School of Science and Technology, Nottingham Trent University, Nottingham, UK. FAU - Durrant, Lindy AU - Durrant L AD - Scancell Ltd, Biodiscovery Institute, University of Nottingham, University Park, Nottingham, UK. FAU - McArdle, Stephanie E AU - McArdle SE AD - John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK. AD - Centre for Health, Ageing and Understanding Disease, School of Science and Technology, Nottingham Trent University, Nottingham, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210919 PL - United States TA - Immunol Cell Biol JT - Immunology and cell biology JID - 8706300 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A2 Antigen) RN - 0 (Vaccines, DNA) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) SB - IM MH - Animals MH - Antigens, Neoplasm/*immunology MH - *Cancer Vaccines/immunology MH - DEAD-box RNA Helicases/*immunology MH - Epitopes, T-Lymphocyte MH - HLA-A2 Antigen MH - Humans MH - Male MH - Mice MH - T-Lymphocytes MH - *Triple Negative Breast Neoplasms/genetics/therapy MH - *Vaccines, DNA/immunology OTO - NOTNLM OT - helicase antigen OT - metastasis OT - treatment OT - triple-negative breast cancer OT - vaccine EDAT- 2021/06/10 06:00 MHDA- 2021/10/26 06:00 CRDT- 2021/06/09 08:54 PHST- 2021/04/28 00:00 [revised] PHST- 2021/05/27 00:00 [revised] PHST- 2021/06/04 00:00 [revised] PHST- 2020/02/25 00:00 [received] PHST- 2021/06/07 00:00 [accepted] PHST- 2021/06/10 06:00 [pubmed] PHST- 2021/10/26 06:00 [medline] PHST- 2021/06/09 08:54 [entrez] AID - 10.1111/imcb.12485 [doi] PST - ppublish SO - Immunol Cell Biol. 2021 Oct;99(9):972-989. doi: 10.1111/imcb.12485. Epub 2021 Sep 19.