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A Novel HAGE/WT1-ImmunoBody® Vaccine Combination Enhances Anti-Tumour Responses When Compared to Either Vaccine Alone

Almshayakhchi, Rukaia; Nagarajan, Divya; Vadakekolathu, Jayakumar; Guinn, Barbara Ann; Reeder, Stephen; Brentville, Victoria; Metheringham, Rachael; Pockley, A. Graham; Durrant, Lindy; McArdle, Stephanie

Authors

Rukaia Almshayakhchi

Divya Nagarajan

Jayakumar Vadakekolathu

Stephen Reeder

Victoria Brentville

Rachael Metheringham

A. Graham Pockley

Lindy Durrant

Stephanie McArdle



Abstract

Many cancers, including myeloid leukaemia express the cancer testis antigen (CTA) DDX43 (HAGE) and/or the oncogene Wilms’ tumour (WT1). Here we demonstrate that HAGE/WT1-ImmunoBody® vaccines derived T-cells can kill ex-vivo human CML cell lines expressing these antigens and significantly delay B16/HHDII+/DR1+/HAGE+/WT1+ tumour growth in the HHDII/DR1 mice and prolonged mouse survival in the prophylactic setting in comparison to non-immunised control mice. We show that immunisation of HHDII/DR1 mice with HAGE- and WT1-ImmunoBody® DNA vaccines in a prime-boost regime in two different flanks induce significant IFN-γ release by splenocytes from treated mice, and a significant level of cytotoxicity against tumour targets expressing HAGE/WT1 in vitro. More importantly, the combined HAGE/WT1 ImmunoBody® vaccine significantly delayed tumour growth in the B16/HHDII+/DR1+/HAGE+/WT1+ tumour model and prolonged mouse survival in the prophylactic setting in comparison to non-immunised control mice. Overall, this work demonstrates that combining both HAGE- and WT1-ImmunoBody® into a single vaccine is better than either vaccine alone. This combination vaccine could be given to patients whose cancer expresses HAGE and WT1 in parallel with existing therapies in order to decrease the chance of disease progression and relapse.

Citation

Almshayakhchi, R., Nagarajan, D., Vadakekolathu, J., Guinn, B. A., Reeder, S., Brentville, V., …McArdle, S. (2021). A Novel HAGE/WT1-ImmunoBody® Vaccine Combination Enhances Anti-Tumour Responses When Compared to Either Vaccine Alone. Frontiers in Oncology, 11, https://doi.org/10.3389/fonc.2021.636977

Journal Article Type Article
Acceptance Date May 14, 2021
Online Publication Date Jun 28, 2021
Publication Date Jun 28, 2021
Deposit Date Jun 28, 2021
Publicly Available Date Jul 5, 2021
Journal Frontiers in Oncology
Electronic ISSN 2234-943X
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 11
Article Number 636977
DOI https://doi.org/10.3389/fonc.2021.636977
Keywords WT1; ImmunoBody®; Immunotherapy; HAGE; Cancer vaccine combination; HHDII/DR1 mice
Public URL https://hull-repository.worktribe.com/output/3777864

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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/

Copyright Statement
Copyright © 2021 Almshayakhchi, Nagarajan, Vadakekolathu, Guinn, Reeder, Brentville, Metheringham, Pockley, Durrant and McArdle. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.







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