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

Xue, Wei; Metheringham, Rachael L.; Brentville, Victoria A.; Gunn, Barbara; Symonds, Peter; Yagita, Hideo; Ramage, Judith M.; Durrant, Lindy

Authors

Wei Xue

Rachael L. Metheringham

Victoria A. Brentville

Barbara Gunn

Peter Symonds

Hideo Yagita

Judith M. Ramage judith.ramage@nottingham.ac.uk

Lindy Durrant Lindy.durrant@nottingham.ac.uk



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.

Journal Article Type Article
Publication Date Jun 15, 2016
Journal Oncoimmunology
Print ISSN 2162-4011
Electronic ISSN 2162-402X
Publisher Taylor & Francis
Peer Reviewed Peer Reviewed
Volume 5
Issue 6
Article Number e1169353
APA6 Citation Xue, W., Metheringham, R. L., Brentville, V. A., Gunn, B., Symonds, P., Yagita, H., …Durrant, L. (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), doi:10.1080/2162402X.2016.1169353
DOI https://doi.org/10.1080/2162402X.2016.1169353
Keywords Cancer immunotherapy; CD4C T cells; CD8C T cells; targeting antigen-presenting cells; NY-ESO-1
Publisher URL https://www.ncbi.nlm.nih.gov/pubmed/27471648
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc/4.0
Additional Information Supplemental data for this article can be accessed on the publisher’s website.

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc/4.0





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