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STING Activators as Therapy for Cancer

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41CA250629-01A1
Agency Tracking Number: R41CA250629
Amount: $252,064.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 101
Solicitation Number: PA19-270
Timeline
Solicitation Year: 2019
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-09-17
Award End Date (Contract End Date): 2021-08-31
Small Business Information
1951 NW 7TH AVE STE 600
Miami, FL 33136-1128
United States
DUNS: 002058614
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 GLEN BARBER
 (305) 646-8103
 glenbarber@stinginn.com
Business Contact
 GLEN BARBER
Phone: (305) 646-8103
Email: glenbarber@stinginn.com
Research Institution
 UNIVERSITY OF MIAMI CORAL GABLES
 
1320 S DIXIE HIGHWAY. SUITE 650, LOCATER CODE 2960
CORAL GABLES, FL 33146-2926
United States

 Nonprofit College or University
Abstract

PROJECT SUMMARY
The ability of dying cells to activate antigen presenting cells (APCs) is carefully controlled to avoid unwarranted
inflammatory responses. Thus, tumor cells avoid aggravating APCs by efficiently simulating regular dying cells
which following phagocytosis do not trigger inflammatory responses required for efficient cytotoxic T lymphocyte
(CTL) priming. However, dying tumor cells containing exogenous innate immune agonists such as cytosolic DNA,
potently activate APCs in trans through extrinsic innate immune, STING- dependent signaling to generate potent
CTL activity. In the absence of STING agonists, dying cells were ineffectual in the stimulation of APCs in trans.
Indeed, cytosolic STING activators, including cytosolic DNA and cyclic dinucleotides (CDNs), constitute cellular
danger associated molecular patterns (DAMPs) usually only generated by viral infection or following DNA-
damage events, that can render tumor cells highly immunogenic (make a `coldandapos; tumor `hotandapos;). Taking advantage of
our mechanistic insight and discoveries, we have now developed a new generation of innate immune activators
that trigger STING signaling (referred to as STAVs: STING activators). Tumor cells transfected with STAVs
activated APCs in trans and can generate potent anti-tumor T cell activity. Immunocompetent mice bearing
metastatic syngeneic tumors could be `curedandapos; following inoculation with STAV `loadedandapos; tumor cells. Our strategy
provides a new, simple, inexpensive therapeutic approach for the treatment of cancer. We have recently
published our findings in the journal Cancer CELL (31) and patented our intellectual property through the
University of Miamiandapos;s Office of Technology Transfer (OTT). This technology has been licensed to STINGINN LLC,
to acquire sufficient pre-clinical data to warrant the consideration of clinical trials. For this study, we aim to
evaluate whether our STAV strategy could be useful for the treatment of leukemia (focusing on adult T cell
leukemia/lymphoma [ATLL] and Acute Myeloid Leukemia [AML]). ATLL is a clonal disease, invariably lethal and
there is no cure or vaccine. AML is among the most aggressive of leukemias and only 5-10% of patients over 60
survive up to 5 years using standard treatments. We have developed a murine tumor model for the study of
these diseases. The objective is to procure sufficient data to consider the development of pre-clinical trials for
the treatment of this and ultimately other types of leukemia and lymphoma related cancers.PROJECT NARRATIVE
Tumor cells are notoriously non-immunogenic through their ability to mimic the properties of normal cells which
have naturally evolved to avoid activating the immune system following cell death and phagocytosis. We have
thus developed a new approach to overcome this obstacle and make previously immuno-evasive, inert tumor
cells highly immunogenic. This has been achieved through developing activators of the STING-dependent innate
immune signaling pathway, a strategy which holds considerable promise for the therapeutic treatment of cancer.

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

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