ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Advanced Search

The Novel Polymer Pro-Drug APP-103 Reduces I/R Injury and Improves Graft Function in a Pre-Clinical Renal Transplant Model

K. Minami,1,3 H. Uehara,1,3 A. Elkhal,1,3 A. Weins,3 S. Bae,2,3 J. Reder,4 B. Houser,4 P. Kang,2,3 S. Tullius.1,3

1Transplant Surgery Division, Department of Surgery, Brigham and Women's Hospital, Boston, MA
2Beth Israel Deaconess Medical Center, Boston, MA
3Harvard Medical School, Boston, MA
4Celdara Medical, LLC, Lebanon, NH.

Meeting: 2018 American Transplant Congress

Abstract number: C5

Keywords: Graft function, Ischemia, Kidney transplantation

Session Information

Date: Monday, June 4, 2018

Session Name: Poster Session C: Antigen Presentation

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall 4EF

Related Abstracts
  • The Polymer Pro-Drug APP-103 Mitigates I/R Injury and Improves Graft Function in a Pre-Clinical Renal Transplant Model.
  • Ischemia Reperfusion Injury (IRI) Causes Local Release of Free Heme Which Aggravates Inflammation and Contributes to Delayed Graft Function.

Purpose: Ischemia-reperfusion injury (IRI) is the strongest non-HLA factor that augments allogenicity of transplanted organs. Damage subsequent to IRI is critically linked to an abundance of ROS, including H202 that initiates inflammation and significantly contributes to allograft loss. APPsTM are potent, site-specific, self-limiting therapeutics that mitigate inflammation by reducing localized oxidative stress. Here, we show that APP-103 can mitigates IRI incurred during transplant surgery by reducing inflammation.

Methods: Lew kidneys were stored at 4[deg]C after procurement. Recipients received APP-103 (i.v./15mg/Kg) or vehicle (PBS). Kidney function was assessed by serum creatinine (SCrea) measured at POD1 and 7. Local inflammation was determined by histology and qPCR for pro-and anti-inflammatory cytokines.

Results: APP-103 ameliorated IRI in prior studies of warm ischemia (kidney, heart and limb injury). Here, we demonstrate that APP-103 restores graft function following renal transplantation in syngeneic rat models by early mitigation of inflammatory responses. Recipients treated with APP-103 had 40% improved graft function (SCrea at day 1). Pathological analysis confirmed a significant reduction in interstitial fibrosis and tubular atrophy on POD1 and 7. Prolonged cold ischemia had been mitigated by APP-103 with significantly SCrea reductions. Treatment with APP-103 resulted in reduced intragraft mRNA levels of pro-inflammatory cytokines TNF-a and IL-6, inhibition of T cell proliferation cytokine IL-2; notably a significant increase of the anti-inflammatory cytokine IL-10 was observed. Flow cytometry revealed a decrease in surface expression of activation and maturation markers including CD40, CD80, and CD86 on DCs treated with APP-103 during stimulation with LPS. Moreover, frequencies of CD4+ and CD8+ IFNγ+ cells were significantly reduced when DCs were cocultivated in presence of APP-103 suggesting a potential to impact alloimmune responses.

Conclusion: APP-103 is a novel and safe therapeutic that targets on-site ROS showing impressive improvements of graft function and structure while dampening inflammatory responses linked to IRI.

CITATION INFORMATION: Minami K., Uehara H., Elkhal A., Weins A., Bae S., Reder J., Houser B., Kang P., Tullius S. The Novel Polymer Pro-Drug APP-103 Reduces I/R Injury and Improves Graft Function in a Pre-Clinical Renal Transplant Model Am J Transplant. 2017;17 (suppl 3).

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Minami K, Uehara H, Elkhal A, Weins A, Bae S, Reder J, Houser B, Kang P, Tullius S. The Novel Polymer Pro-Drug APP-103 Reduces I/R Injury and Improves Graft Function in a Pre-Clinical Renal Transplant Model [abstract]. https://atcmeetingabstracts.com/abstract/the-novel-polymer-pro-drug-app-103-reduces-i-r-injury-and-improves-graft-function-in-a-pre-clinical-renal-transplant-model/. Accessed March 8, 2021.

« Back to 2018 American Transplant Congress

Most Viewed Abstracts

  • This Week
  • This Month
  • All Time
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Live Related Kidney Transplant Experience in Abuja, Nigeria – First Eight Cases Ever.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • A Decade of Donor-Derived Disease: A Report of the OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC).
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Evidence of a Clinically Significant Drug-Drug Interaction between Cannabidiol and Tacrolimus: A Case Report
  • Kidney Dialysis after Heart Transplantation: The Short and Long Term Outcomes

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2021 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy

loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.