Muckenhuber, Moritz and Mucha, Jasmin and Mengrelis, Konstantinos and How, Christopher and Reindl-Schwaighofer, Roman and Heinzel, Andreas and Kainz, Verena and Worel, Nina and Berlakovich, Gabriela and Edinger, Matthias and Oberbauer, Rainer and Wekerle, Thomas (2023) Optimum timing of antithymocyte globulin in relation to adoptive regulatory T cell therapy. AMERICAN JOURNAL OF TRANSPLANTATION, 23 (1). pp. 84-92. ISSN 1600-6135, 1600-6143
Full text not available from this repository. (Request a copy)Abstract
Reducing the recipient's T cell repertoire is considered to increase the efficacy of regulatory T cell (Treg) therapy. This necessitates timing the administration of antithymocyte globulin (ATG) early enough before adoptive cell therapy (ACT) so that residual serum ATG does not deplete the transferred Tregs. The optimum time point in this regard has not been defined. Herein, we report the effects of residual serum ATG on the viability of an in vitro expanded Treg cell product used in a clinical trial of ACT in kidney transplant recipients (NCT03867617). Patients received ATG monotherapy (either 6 or 3 mg/kg body weight) without concomitant immunosuppression 2 to 3 weeks before transplantation and Treg transfer. An anti-ATG immunoglobulin G (IgG) immune response was elicited in all patients within 14 days. In turn, the elimination of total and Treg-specific ATG was accelerated substantially over control patients receiving the same dose of ATG with concomitant immunosuppression. However, ATG serum concentrations of <1 mu g/mL, which had previously been reported as subtherapeutic threshold, triggered apoptosis of Tregs in vitro. Therefore, ATG levels need to decline to lower levels than those previously thought for efficacious Treg transfer. In 5 of 6 patients, such low levels of serum ATG considered safe for Treg transfer were reached within 2 weeks after ATG administration.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSPLANTATION; PHARMACOKINETICS; THYMOGLOBULIN; SENSITIZATION; STRATEGIES; INDUCTION; APOPTOSIS; MEMORY; translational research; science; immunosuppression; immune modulation; kidney transplantation; nephrology; cellular transplantation (nonislet); immunosuppressive regimens -induction; immunosuppressant-polyclonal preparations; rabbit antithymocyte globulin; immunosuppressant-fusion proteins and; monoclonal antibodies; belatacept; tolerance; clinical |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Jan 2024 07:45 |
| Last Modified: | 31 Jan 2024 07:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60078 |
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