Accession Number:

AD1004940

Title:

The Johns Hopkins RTR Consortium: A Collaborative Approach to Advance Translational Science and Standardize Clinical Monitoring of Restorative Transplantation

Descriptive Note:

Technical Report,15 Sep 2014,14 Sep 2015

Corporate Author:

Johns Hopkins University Baltimore United States

Personal Author(s):

Report Date:

2015-10-01

Pagination or Media Count:

18.0

Abstract:

For many devastating combat and civilian injuries where conventional reconstruction is inadequate, vascularized composite allotransplantation VCA has become a viable alternative. However, the toxicities and adverse effects of high dose immunosuppressive drugs have curtailed wider application. Thus the purpose of this project is to develop novel clinically relevant immunosuppression sparing regimens allowing for immunomodulation and tolerance induction after VCA using a translational large animal model. During the current reporting period the group continue to study a belatacept-based protocol to enable calcineurin inhibitor minimization Aim 1 after heterotopic swine hind-limb allotransplantation across a full SLA mismatch and furthermore set out to examine the efficacy of transitioning to belatacept CTLA4-Ig maintenance therapy from a calcineurin inhibitor based immunosuppression regimen Aim 2. In year 2 of the study, all animals in Aim 1 and 2 have undergone transplantation. All group I animals died prematurely due to infectious complications related to high dose tacrolimus treatment.23 animals that received sub-therapeutic tacrolimus group II have rejected their grafts. 35 animals who received belatacept in addition to low dose tacrolimus group III have achieved long term graft survival 230 days. All group IV and V animals that received 60 days of tacrolimus and proceeded to either weaning immunosuppression or transition to belatacept have not shown evidence of rejection thus far. Overall, our preliminary results indicate that belatacept is highly effective as a biologic agent in maintaining allograft survival without the need for conventional high dose calcineurin inhibitor based immunosuppression. Furthermore, the long term graft survival off of immunosuppression for animals treated with low dose tacrolimus suggest that the vascularized bone component of the composite graft may have a robust immunomodulatory effect. Additional clinical follow-u

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Distribution Statement:

APPROVED FOR PUBLIC RELEASE