Ckade of CTLA4, PD1, or PDL1. Conclusions These information demonstrate feasibility of a novel chimeric

Ckade of CTLA4, PD1, or PDL1. Conclusions These information demonstrate feasibility of a novel chimeric fusion protein platform, delivering checkpoint blockade and TNF superfamily costimulation inside a single molecule. Signal replacement of CD47 by CD40L may perhaps uniquely poise DCs/macrophages inside the tumor microenvironment for activation and cross-presentation of tumor DAPK Source antigens following enhanced tumor cell phagocytosis. P520 All-natural killer (NK) cells orchestrate the antitumor activities of Listeria monocytogenes (Lm)-based immunotherapy Rachelle Kosoff, PhD1, Lauren Pettit, MS1, Nithya Thambi, MS1, Kimberly Ramos, Bachelors in Smaller Animal Science1, Jeff Jones1, Skye Na+/Ca2+ Exchanger web Kuseryk1, Robert Petit, PhD1, Michael Princiotta, MS, PhD1, Kim Jaffe, PhD1, Sandy Hayes, PhD2 1 ADVAXIS, INC, Princeton, NJ, USA; 2Advaxis Immunotherapies, Inc, Princeton, NJ, USA Correspondence: Sandy Hayes ([email protected]) Journal for ImmunoTherapy of Cancer 2018, six(Suppl 1):P520 Background Advaxis’ Lm-based immunotherapies are antigen-based immunotherapies which might be created to elicit tumor antigen- particular T cell effectors that recognize and kill tumor cells. However, since the tumor antigens are delivered by a bacterial vaccine vector, innate cytotoxic effectors, such as NK cells, might also be recruited to play a function in controlling tumor growth. The objective of this study would be to decide irrespective of whether and how NK cells contribute towards the antitumor activities of Lm-based immunotherapy.P519 Agonist redirected checkpoint platform (ARC), engineering bifunctional fusion proteins (SIRP -Fc-CD40L), for cancer immunotherapy George Fromm, PhD1, Suresh de Silva, PhD2, Taylor Schreiber, MD, PhD2 1 Shattuck Labs, Inc, Apex, NC, USA; 2Shattuck Labs, Inc., Durham, NC, USA Correspondence: George Fromm ([email protected]) Journal for ImmunoTherapy of Cancer 2018, six(Suppl 1):PJournal for ImmunoTherapy of Cancer 2018, 6(Suppl 1):Web page 272 ofMethods Tumor development inhibition was evaluated in C57BL/6 mice that were implanted with human papillomavirus (HPV)16+ TC-1 tumor cells after which immunized on days 8, 15 and 22 following tumor implantation with PBS or with axalimogene filolisbac (AXAL), an Lm-based immunotherapy expressing the HPV16 E7 protein. To in vivo deplete NK cells, anti-asialo GM1 antibody (Ab) was administered 1 day before tumor implantation and at 3-day intervals throughout the PBS or AXAL therapy regimen. For mechanistic research, flow cytometric analysis and immune-related gene profiling of tumor infiltrating leukocytes (TILs) were performed at different time points soon after tumor implantation. Outcomes We first compared intratumoral NK cell frequency and maturation in PBS- and AXAL-treated mice. Even though the percentages of intratumoral NK cells in PBS- and AXAL-treated mice have been equivalent, NK cells in tumors of AXAL-treated mice were a lot more functionally mature, according to their high expression of CD11b and granzyme A, than NK cells in tumors of PBS-treated mice. To ascertain irrespective of whether AXAL-induced NK cell activity was expected for AXAL-mediated tumor handle, we made use of anti-asialo GM1 Ab to in vivo deplete NK cells. In AXAL-treated mice, NK cell depletion resulted within a full loss of tumor development inhibition. Phenotypic and functional analyses of TILs revealed impaired dendritic cell (DC) maturation and considerably decreased infiltration of functional HPV- certain CD8+ T cells in NK cell-depleted AXAL-treated mice when compared with AXAL-treated mice. Gene profiling and pathway evaluation showed that the genes si.