Competent animal models. Furthermore, SIRP-Fc-VVs readily infect tumor cells and induce phagocytosis by macrophages. Therefore,

Competent animal models. Furthermore, SIRP-Fc-VVs readily infect tumor cells and induce phagocytosis by macrophages. Therefore, arming oncolytic viruses for example VVs with SIRP-Fc has the prospective to improve their antitumor activity. P309 Selective activation of innate immune responses by the Ad11/Ad3 chimeric oncolytic group B adenovirus enadenotucirev Hugo Calderon1, Sam Illingworth1, Alice Brown1, Kerry Fisher1, Len Seymour2, Brian Champion1 1 PsiOxus Therapeutics Ltd, Abingdon, England, UK; 2Oxford University, Oxford, England, UK Correspondence: Brian Champion ([email protected]) Journal for ImmunoTherapy of Cancer 2016, four(Suppl 1):P309 Background Oncolytic viruses (OVs) are characterized by their ability to selectively infect and kill tumor cells. Far more recently they’ve been exploited for their capacity to be encoded with, and locally provide, a variety of payloads which includes immunotherapeutic transgenes to improve immune responses against the tumor. Viral properties of OVs may well also have the ability to engage the innate immune system and therefore influence the suppressive nature in the tumor microenvironment. A far better understanding of these interactions may perhaps help guide both the rational design and style of `armed’ viruses at the same time because the design of methods for combining with other immunotherapies. Enadenotucirev (EnAd) is actually a chimeric Ad11/Ad3 group B oncolytic adenovirus under improvement for the systemic treatment of metastatic carcinomas. As opposed to the group C virus Ad5, EnAd doesn’t bind to cells via the Vehicle receptor but as an alternative uses CD46 which is expressed by innate immune cells. Approaches We’ve been evaluating the effect of EnAd on innate immune responses making use of in vitro immature human monocyte-derived dendritic cells (DC) as a model suppressive phenotype APC. Benefits EnAd induced up-regulation of surface activation markers and induced the production of pro-inflammatory cytokines. Additional mechanistic experiments, comparing the effects of EnAd to those of Ad5 indicated that the activation was selective for EnAd, was particle-mediated and dependent on CD46 binding. In an effort to have an understanding of the functional implications downstream of these interactions, T cell activation and phenotype was assessed working with an allogeneic mixed lymphocyte reaction method. EnAd-treated DCs selectively stimulated stronger T cell responses, like enhanced IFNg production. The data supports EnAd as a fantastic candidate OV for steering the SGK1 Inhibitor Accession response of T cells activated within the tumor towards a Th1 phenotype for enhanced effector responses. Conclusions Therefore, also as its potent oncolytic properties, EnAd particles may possibly also function in the tumor microenvironment to assist drive functional adaptive immune responses by inducing proinflammatory phenotype APCs, which must also synergize RGS19 Inhibitor supplier properly with other immunotherapy approaches.P310 CD40L-armed oncolytic LOAd viruses handle development of CD40+ T24 bladder cancer via each oncolysis and CD40-mediated apoptosis Emma Eriksson1, Jessica Wenthe1, Ann-Charlotte Hellstr 1, Gabriella Paul-Wetterberg1, Angelica Loskog2 1 Uppsala University, Uppsala, Sweden; 2Uppsala University, Lokon Pharma AB, Uppsala, Sweden Correspondence: Emma Eriksson ([email protected]) Journal for ImmunoTherapy of Cancer 2016, four(Suppl 1):P310 Background CD40-CD40L signaling is often a highly effective pathway that can be utilized in cancer immunotherapy. CD40 stimulation of immune cells drives a Th1 anti-tumor response but CD40 stimulation on tumor cells can cause enhanced tum.