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Targeted Nanotherapy to Donor Organ Endothelia Modulates Early Immune Responses and Protects Against Late Graft Failure

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41EB028150-01
Agency Tracking Number: R41EB028150
Amount: $225,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIBIB
Solicitation Number: PA17-303
Solicitation Year: 2017
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-09-20
Award End Date (Contract End Date): 2019-09-19
Small Business Information
Mount Pleasant, SC 29464-3533
United States
DUNS: 079606373
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 (843) 793-7972
Business Contact
Phone: (216) 832-5503
Research Institution
CHARLESTON, SC 29403-5120
United States

 Nonprofit college or university

Transplantation is an accepted and highly successful therapy for end stage organ diseaseWhile success rates and survival
have risen steadilydue largely to improved immunosuppression regimesthere is a growing appreciation that damage and
inflammation that occur early in the life of the graftsignificantly impact chronic rejection and thus long term survivalCentral to these early event injuries is the activation of donor endothelial cellsECsthatupon reperfusionpromote
inflammationcytokine releaseand priming and proliferation of graft infiltrating memory T cellsModulation of the
endothelium prior to transplantation may reduce early graft injury and chronic rejectionIn an EC T cell co culture
systemEC pre treatment with the immunosuppressive drugrapamycinresults in reduced EC activationreduced alloreactive memory T cell activationand further skews the T cell response to a graft protective regulatory T cell phenotypeall factors that would protect the organ from chronic rejectionIn this proposalwe optimize a means to effectively deliver
rapamycin to the donor organ endothelium prior to transplantation in a clinically relevant paradigmWeToleRaM
NanotechLLCwww toleramnano comhave designeddevelopedand characterized a novel EC targeted drug delivery
vehiclereferred to as Targeted Rapamycin MicelleTRaMthat we have shown improves cellular and graft penetrationWe hypothesize that organ pre treatment with Targeted Rapamycin Micelle will improve rapamycin uptakehalf lifeand significantly impair EC activationcytokine releaseand T cell co stimulationthereby reducing early graft injury
to protect against the development of chronic rejection Project Narrative
While organ transplantation is effectivethe overall success of the transplantation is adversely affected by the quality of
the donor organ and the prevalence and proliferation of memory T cells which are unresponsive to conventional
immunosuppressive regimesHerewe propose to utilize a novel bioengineered therapeutic delivery system to pretreat
donor organsspecifically the donor endotheliumwith rapamycin to reduce endothelial activation and endothelial T cell
co stimulatory activity to optimize transplantation outcome

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

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