SCIB2, an antibody DNA vaccine encoding NY-ESO-1 epitopes, induces potent antitumor immunity which is further enhanced by checkpoint blockade

Xue, Wei and Metheringham, Rachael L. and Brentville, Victoria A. and Gunn, Barbara and Symonds, Peter and Yagita, Hideo and Ramage, Judith M. and Durrant, Lindy (2016) SCIB2, an antibody DNA vaccine encoding NY-ESO-1 epitopes, induces potent antitumor immunity which is further enhanced by checkpoint blockade. Oncoimmunology, 5 (6). e1169353/1-e1169353/13. ISSN 2162-402X

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Abstract

Checkpoint blockade has demonstrated promising antitumor responses in approximately 10-40% of patients. However, the majority of patients do not make a productive immune response to their tumors and do not respond to checkpoint blockade. These patients may benefit from an effective vaccine that stimulates high-avidity T cell responses in combination with checkpoint blockade. We have previously shown that incorporating TRP-2 and gp100 epitopes into the CDR regions of a human IgG1 DNA (ImmunoBody®: IB) results in significant tumor regression both in animal models and patients. This vaccination strategy is superior to others as it targets antigen to antigen-presenting cells and stimulates high-avidity T cell responses. To broaden the application of this vaccination strategy, 16 NY-ESO-1 epitopes, covering over 80% of HLA phenotypes, were incorporated into the IB (SCIB2). They produced higher frequency and avidity T cell responses than peptide vaccination. These T cells were of sufficient avidity to kill NY-ESO-1-expressing tumor cells, and in vivo controlled the growth of established B16-NY-ESO-1 tumors, resulting in long-term survival (35%). When SCIB2 was given in combination with Treg depletion, CTLA-4 blockade or PD-1 blockade, long-term survival from established tumors was significantly enhanced to 56, 67 and 100%, respectively. Translating these responses into the clinic by using a combination of SCIB2 vaccination and checkpoint blockade can only further improve clinical responses.

Item Type: Article
Additional Information: Supplemental data for this article can be accessed on the publisher’s website.
Keywords: Cancer immunotherapy; CD4C T cells; CD8C T cells; targeting antigen-presenting cells; NY-ESO-1
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
Identification Number: https://doi.org/10.1080/2162402X.2016.1169353
Depositing User: Durrant, Lindy
Date Deposited: 14 Feb 2018 16:14
Last Modified: 31 Aug 2018 18:08
URI: http://eprints.nottingham.ac.uk/id/eprint/49788

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