ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2022 American Transplant Congress
    • 2021 American Transplant Congress
    • 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
    • 2021 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
  • Search

AT-1501, a Novel and Clinically Applicable CD40L Specific Monoclonal Antibody, Promotes Islet Allograft Survival in Nonhuman Primates

D. Berman1, N. Kenyon1, M. Willman1, A. Gill2, S. Perrin3, C. Ricordi1

1University of Miami, Miami, FL, 2ALS Therapy Development Institute, Cambridge, MA, 3Novus Therapeutics, Irvine, CA

Meeting: 2021 American Transplant Congress

Abstract number: 343

Keywords: Alloantibodies, Co-stimulation, Inflammation, T cells

Topic: Basic Science » Islet Cell and Cell Transplantation

Session Information

Session Name: Xenotranplantation and Preclinical Studies

Session Type: Rapid Fire Oral Abstract

Date: Tuesday, June 8, 2021

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

 Presentation Time: 6:05pm-6:10pm

Location: Virtual

*Purpose: Immune intervention with a CD40L specific monoclonal antibody (mAb, Hu5c8, Biogen) has previously been shown to safely and effectively prevent islet allograft (IA) rejection in three nonhuman primate (NHP) models. Clinical development for IA was precluded due to occurrence of thromboembolic complications (TE). AT-1501 (Novus Therapeutics) was engineered to preserve immune modulatory potential while avoiding TE and was shown to be safe in NHP. We tested AT-1501 in a diabetic cynomolgus monkey IA model, alone or in combination with additional agents.

*Methods: A total of 5 groups (n=2 each, recipients MHC mismatched to the islet donor) received 10,000 or more IEQ/kg into the liver. An AT-1501 monotherapy group, with 25 mg/kg given IV on POD -1, 0, 3, 10, 18, 23 and 28 and every 14 days thereafter, was included to verify the previously observed efficacy of anti-CD40L. The other 4 groups incorporated T cell depletion with thymoglobulin (Thy; 5 peri-transplant doses at 5 mg/kg each), with a standard of care (SOC) group also receiving FK506 and rapamycin (target trough levels 8-12 and 4-6 ng/ml, respectively) plus Enbrel (0.8 mg/kg IV on POD 0 and 0.4 mg/kg SC on POD 3, 7, 10). For the remaining 3 groups, AT-1501 was given as described for monotherapy but with additional doses on POD -2, -1 and 7. One group involved immune suppression as for the SOC group but replacing FK506 with AT-1501.

*Results: As compared to recipients in the SOC group, animals in the 4 AT-1501 treated groups had lower fasting blood glucose (FBG, 63 ± 14 vs 97 ± 19 mg/dl; p=0.04) and higher fasting (4.5 ± 0.1 vs 1.7 ± 0.1 ng/mg; p = 0.014) and stimulated (9.0 ± 2.1 vs 2.6 ± 0.4 ng/mg; p = 0.010) C-peptide/FBG. Animals in the AT-1501 groups experienced: greater weight gain, none to minimal CMV viral infection and down-regulation of anti-donor specific CD3/4 and 3/8 central memory T cells (at 2 months post-transplant). No class I or II alloantibody was observed.

*Conclusions: AT-1501 appears to be a safe and effective agent to promote islet engraftment and long-term survival and a promising tool for tolerance induction strategies.

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Berman D, Kenyon N, Willman M, Gill A, Perrin S, Ricordi C. AT-1501, a Novel and Clinically Applicable CD40L Specific Monoclonal Antibody, Promotes Islet Allograft Survival in Nonhuman Primates [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/at-1501-a-novel-and-clinically-applicable-cd40l-specific-monoclonal-antibody-promotes-islet-allograft-survival-in-nonhuman-primates/. Accessed May 9, 2025.

« Back to 2021 American Transplant Congress

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 © 2013-2025 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use | Cookie Preferences