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Rapid Non-Viral Platform for Generation of Genetically Modified T Cells for Therapy

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 6R44CA233143-03
Agency Tracking Number: R44CA233143
Amount: $1,406,084.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: 100
Solicitation Number: PA17-302
Solicitation Year: 2017
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-06-01
Award End Date (Contract End Date): 2021-05-31
Small Business Information
Minneapolis, MN 55413-2610
United States
DUNS: 087248183
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (612) 656-4576
Business Contact
Phone: (612) 656-4576
Research Institution

Cancer immunotherapy, particularly genetically engineered adoptive T cell transfer, has shown great potential
for the treatment of cancer patients. The use of T cells engineered to express a specific T cell receptor (TCRs)
or chimeric antigen receptor (CARs) to treat cancer has generated durable cures for many cancer patients and
has resulted in the first FDA approved CAR-T therapy to treat childhood acute lymphoblastic leukemia in 2017.
Most gene therapies rely on viral methods to genetically modify human primary cells. However, viral delivery
method is expensive, poorly reproducible and associated with several safety concerns including insertion in or
near genes that may cause malignancy and generation of replication competent virus. Thus, non-viral DNA
delivery methods, such as Sleeping Beauty and piggyBac, have been employed to generate CAR T cells.
Although these non-viral delivery methods have the advantage of lower cost, immunogenicity, and regulatory
considerations, they have been limited by their low transposition efficiency in primary human hematopoietic cells.
In this application, we propose to rationally optimize a recently discovered transposon, TcBuster to deliver CARs
to T cells. To this end, we further enhance our already very active hyperactive mutants of the TcBuster
transposase and optimize the delivery of the transposon into cells. Following optimization of the TcBuster
transposon system, we will combine these improvements with our proprietary methods to transfect T-cells
efficiently and safely, and test the immunotherapeutic effectiveness of TcBuster delivered CAR into T cells. The
successful completion of this project will result in the comprehensive methods to produce CAR T cells delivered
by TcBuster which we will license to pharmaceutical companies to produce highly efficient CAR-T
immunotherapy. More broadly, these methods could be expanded beyond immunotherapeutic cancer
applications to various infectious diseases in which gene delivery by TcBuster in T cells could be advantageous.This proposal describes a novel method for delivering permanent gene transfer into human primary T cells for
achieving safe, efficient and cost-effective cellular based immunotherapy. We propose to rationally optimize the
activity of the TcBuster transposonto deliver a chimeric antigen receptor (CAR) safely and efficiently into T cells
to improve the immunotherapeutic cancer activity of these cells. The development of such innovative gene
delivery methods will not only create an effective CAR-T based cancer therapy, but also allow for the
advancement of additional non-cancer T cell based applications such as controlling bacterial, fungal, protozoan
or viral infection.

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

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