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Overcoming anti-PD-1 resistance by systemic delivery of an oncolytic adenovirus that targets TGF-beta

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41CA224504-01A1
Agency Tracking Number: R41CA224504
Amount: $299,956.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 102
Solicitation Number: PA17-303
Solicitation Year: 2017
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-07-03
Award End Date (Contract End Date): 2019-06-30
Small Business Information
Houston, TX 77010-1014
United States
DUNS: 963413609
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (847) 570-2378
Business Contact
Phone: (832) 431-3555
Research Institution
EVANSTON, IL 60201-1613
United States

 Domestic Nonprofit Research Organization

Project Summary
The overall goal of this proposal is to test a novel systemic Adenoviral therapy that targets transforming
growth factorTGFand reverses anti PDresistance to treat advanced breast and lung cancersThis
STTR grant application illustrates the synergistic relationship between DrPrem Sethinventor of a novel
TGFdecoyand MultiVir Inca leader in clinical development of gene based therapeuticsDrSeth has
developed novel adenoviral vectors targeting TGFa well recognized but largely undruggable oncology
targetIn additionhe has created a platform that can be delivered systemicallyand specifically targets
oncolytic adenoviral vectors to tumorsThis oncolytic adenovirus vector has been engineered to reduce
toxicity and the vector targets tumor cells via tumor specific peptideDrSeth has recently expanded his
studies to examine if oncolytic adenoviruses targeting TGFcan overcome resistance to checkpoint inhibitor
therapiesCKIsuch as PDCTLAAlthough clinical studies have demonstrated encouraging response
rates and long term survival in some breast cancer patientsit is clear that most patients do not respond or
develop resistance to CKIsBecause of the critical role that TGFplays in immunosuppressionangiogenesis and epithelial mesenchymal transitiona novel approach to overcoming CKI resistance would
be to block TGFusing a decoy receptorWe will use two well characterized tumor modelsa mammary
tumor and a lung cancer model in immunocompetent mice to conduct the following two Specific AimsIn Aimwe will examine if the intravenous administration of our vector results in reduced liver uptakeenhanced
tumor uptake and targets TGFpathways in the tumors and tumor microenvironmentAimwill determine if
the intravenous delivery of vector can enhance efficacy of anti PDmediated therapyand inhibit tumor
growth and spontaneous metastases in an anti PDresistantTmouse mammary and Lewis lung cancer
mouse mammary tumor modelWe believe that the pre clinical research described here is critical to bring
our therapeutic vector forward to its clinical evaluationThe proposed research aligns with MultiVirandapos s
research interestsMultiVir Incis highly supportive of this PhaseSTTR grant proposaland if successfulplans to continue our collaborations with DrSethleading to the conduct of IND enabling studies as part of
potential Phaseproposal NARRATIVE
This proposal describes the development of a noveltumor targeted TGFinhibitor delivered by
adenoviral gene therapy that induces anti tumor immunity and reverses resistance to other
immunotherapies termed immune checkpoint inhibitorsanti PDThe approach will initially be
developed for the treatment of metastatic breast and lung cancersSuccessful completion of this
project will lead to future clinical trials in breast and lung cancer patients with unmet medical needsThis drug candidate may also find future application in the treatment other types of cancers

* Information listed above is at the time of submission. *

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