A novel immuno-oncolytic viral therapy for the treatment of non-small cell lung carcinoma

Project Summary Abstract The goal of this project is to complete the pre clinical and translational studies necessary to prepare a novel oncolytic viralOVtherapyWO Sfor clinical evaluation in non small cell lung cancerNSCLCNSCLC is the predominate form of lung cancerwhich is the leading cause of cancer death in the United StatesRecentlyimmunotherapies have emerged as a potential new treatment approach in NSCLC but have been limited by low response rates and designated primarily for use in second line treatmentHoweverthe ability of OVs to exploit the immune system has been demonstrated in other solid tumor typessuch as melanomaand so they hold great promise for use in NSCLCespecially if effective systemic delivery were possibleOncolytic viruses have the potential to incorporate multiple features into a single viral backboneto target cancer cells directlyto induce cell deathto overcome localized immune suppression within the tumorand to boost the anti tumor adaptive immune response while evading anti viral immune responsesTo dateno effective OV therapies have been developed for use in NSCLCprimarily due to the need to delivery most OVs directly into the tumora delivery mechanism that is often not feasible in lung cancerWO Srepresents a next generation of OV therapiesand has been engineered to contain multiple genetic modifications and expresses several transgeneswhichcollectivelyovercome many of the limitations facing previous generations of OVsModifications in WO Sallow for greatly enhanced intravenous administrationincreased tumor selective viral replicationas well as targeting of activated STATa protein that is a key driver of many of the hallmarks of cancerFurthermoreWO Sovercomes immune suppression in the tumorPrevious pre clinical work has demonstrated WO S andapos s mechanism of action and potency against tumorsincluding mouse models of lung cancerWe believe that this therapy has significant potential to advance the treatment of NSCLCand advancing WO Sto clinical testing is of importanceThe work described in this current proposal is specifically aimed at completing the studies necessary to prepare for clinical evaluationAs suchwe will demonstrate that our existing manufacture process can be used to create WO Sat clinical grade and in sufficient quantities for use in clinical testingwith the ultimate goal of producing an economically viable productIn additionwe will complete the FDA mandated safety and toxicology testing through a series of mouse studiesWe will develop all assays necessary to confirm the clinical productWO Sis as intendedand these will be transferred to a contract manufacturing facility where a viral bank of WO Swill be created for use as seed material in all future manufacturing runs for clinical testing as well as eventual commercial useIn additionmouse studies will be run to define the optimal treatment regimen for the use of WO Salone or in combination with approved immunotherapies in the treatment of NSCLCAs a resultfirst in man studies will be possible soon after the completion of this proposal Project Narrative Immunotherapy is a new approach to treating non small cell lung carcinomashowing some key initial successesWO Sis a novel viral immuno oncolytic therapyengineered to be systemically deliverable to the tumor in a targeted fashionas well as to enhance immunotherapeutic activity and to increase viral replication and spreadThese features target many genetic alterations commonly seen in non small cell lung cancermaking this vector a highly promising novel approach to treating this disease