Competent animal models. In addition, SIRP-Fc-VVs readily infect tumor cells and induce phagocytosis by macrophages. Therefore, arming oncolytic viruses which include VVs with SIRP-Fc has the possible to enhance their antitumor activity. P309 Selective activation of innate immune responses by the Ad11/Ad3 chimeric oncolytic group B CCL15 Proteins Storage & Stability adenovirus enadenotucirev Hugo Calderon1, Sam Illingworth1, Alice Brown1, Kerry PDGF-D Proteins site 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, 4(Suppl 1):P309 Background Oncolytic viruses (OVs) are characterized by their capability to selectively infect and kill tumor cells. Far more not too long ago they’ve been exploited for their capacity to become encoded with, and locally provide, several different payloads including immunotherapeutic transgenes to improve immune responses against the tumor. Viral properties of OVs may well also be capable of engage the innate immune technique and thus influence the suppressive nature on the tumor microenvironment. A far better understanding of these interactions may support guide each the rational design of `armed’ viruses also as the design and style of approaches for combining with other immunotherapies. Enadenotucirev (EnAd) can be a chimeric Ad11/Ad3 group B oncolytic adenovirus below improvement for the systemic therapy of metastatic carcinomas. In contrast to the group C virus Ad5, EnAd will not bind to cells via the Automobile receptor but as an alternative makes use of CD46 that is expressed by innate immune cells. Procedures We’ve been evaluating the impact of EnAd on innate immune responses employing in vitro immature human monocyte-derived dendritic cells (DC) as a model suppressive phenotype APC. Results EnAd induced up-regulation of surface activation markers and induced the production of pro-inflammatory cytokines. Further mechanistic experiments, comparing the effects of EnAd to these 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 those interactions, T cell activation and phenotype was assessed employing an allogeneic mixed lymphocyte reaction strategy. EnAd-treated DCs selectively stimulated stronger T cell responses, including enhanced IFNg production. The information supports EnAd as a fantastic candidate OV for steering the response of T cells activated within the tumor towards a Th1 phenotype for enhanced effector responses. Conclusions Therefore, at the same time as its potent oncolytic properties, EnAd particles may also function within the tumor microenvironment to assist drive functional adaptive immune responses by inducing proinflammatory phenotype APCs, which ought to also synergize correctly with other immunotherapy methods.P310 CD40L-armed oncolytic LOAd viruses handle development of CD40+ T24 bladder cancer through 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 usually a highly effective pathway that can be made use of in cancer immunotherapy. CD40 stimulation of immune cells drives a Th1 anti-tumor response but CD40 stimulation on tumor cells can lead to enhanced tum.
