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

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.

Citation

Xue, W., Metheringham, R. L., Brentville, V. A., Gunn, B., Symonds, P., Yagita, H., Ramage, J. M., & 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), Article e1169353. https://doi.org/10.1080/2162402X.2016.1169353

• Journal Article Type: Article
• Acceptance Date: Mar 17, 2016
• Online Publication Date: Jun 15, 2016
• Publication Date: Jun 15, 2016
• Deposit Date: Feb 14, 2018
• Publicly Available Date: Feb 14, 2018
• Journal: Oncoimmunology
• Print ISSN: 2162-4011
• Electronic ISSN: 2162-402X
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Issue: 6
• Article Number: e1169353
• 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
• Public URL: https://nottingham-repository.worktribe.com/output/795112
• Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/27471648
• Additional Information: Supplemental data for this article can be accessed on the publisher’s website.
• Contract Date: Feb 14, 2018