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

Wei Xue ¹, Rachael L Metheringham ¹, Victoria A Brentville ¹, Barbara Gunn ¹, Peter Symonds ¹, Hideo Yagita ², Judith M Ramage ³, Lindy G Durrant ⁴

Affiliations

¹ Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, City Hospital Campus , Nottingham, UK.
² Department of Immunology, Juntendo University School of Medicine , Tokyo, Japan.
³ Academic Department of Clinical Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, City Hospital Campus , Nottingham, UK.
⁴ Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, City Hospital Campus, Nottingham, UK; Academic Department of Clinical Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, City Hospital Campus, Nottingham, UK.

PMID: 27471648
63 References
19 citations

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.

Keywords: CD4+ T cells; CD8+ T cells; Cancer immunotherapy; NY-ESO-1; targeting antigen-presenting cells.

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