title: SCIB2, an antibody DNA vaccine encoding NY-ESO-1 epitopes, induces potent antitumor immunity which is further enhanced by checkpoint blockade.
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.
authors.affiliation: Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, City Hospital Campus , Nottingham, UK.
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.affiliation: Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, City Hospital Campus , Nottingham, UK.
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Metheringham
authors.affiliation: Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, City Hospital Campus , Nottingham, UK.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Brentville
authors.affiliation: Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, City Hospital Campus , Nottingham, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gunn
authors.affiliation: Scancell Limited, Academic Department of Clinical Oncology, University of Nottingham, City Hospital Campus , Nottingham, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Symonds
authors.affiliation: Department of Immunology, Juntendo University School of Medicine , Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.affiliation: Academic Department of Clinical Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, City Hospital Campus , Nottingham, UK.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Ramage
authors.affiliation: 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.
authors.forename: Lindy G
authors.initials: LG
authors.lastname: Durrant
keywords: CD4+ T cells; CD8+ T cells; Cancer immunotherapy; NY-ESO-1; targeting antigen-presenting cells