Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Interleukin-6 is an important inflammatory cytokine. In addition, it acts as a growth factor for B-cells, plasma cells and Th17 cells, inhibiting FoxP3+ Treg cells. These considerations suggest IL-6 may be an important target to reduce inflammation and Th17 mediated inflammation in kidney allografts.
*Methods: Clazakizumab (Vitaeris Inc.) is a humanized monoclonal antibody aimed at the cytokine IL-6. As part of a phase I/II trial of clazakizumab for desensitization, HLA sensitized patients received anti-IL-6, 25mg SC monthly X 6 doses with monitoring of HLA antibody levels and Tregs. Patients were treated pre- and post-transplant with anti-IL-6. Transplanted patients received monthly claza 25mg SC starting 5-7 days post-transplant for 12M. Tregs were determined by flow cytometry as CD4+,CD25+,CD127dim,FoxP3+ cell populations in CD4+ cells. Determinations were made at baseline, at transplantation and day 180 post-transplant.
*Results: Nine patients were transplanted. All patients had previous transplants; 78% had cPRA 99-100%, 67% were B-cell FCMX+ and class II DSA+ @ time of transplant. Mean MFI for HLA cI & cII were: pre-desensitization vs. post claza: cI 13062±3123 vs. 8585±4597 (p=0.05) and cII 13519±2966 vs. 8344±4836 (p =0.03). All DSA+ patients were negative by day 180 post-transplant. Mean Treg values at baseline v. at transplant did not differ (3.2+1.09% v.3.5+1.75%,p=NS). However, were significantly different at day 180 post-transplant (3.2+1.09% v.3.5+1.75% v. 12.6+9.3%, p=0.008)(Figure 1).
*Conclusions: Clazakizumab desensitization reduced HLA cI/cII antibodies and allowed 9/10 highly sensitized patients to receive transplants. In addition, a dramatic increase in Treg cells at day 180 post-transplant was seen while patients were still on anti-IL-6 therapy suggesting that anti-IL-6 may deviate CD4+ T-cell responses to a Treg profile. This may have therapeutic implications for modifying baseline immunosuppression post-transplant.
To cite this abstract in AMA style:Jordan SC, Ge S, Ammerman N, Toyoda M, Huang E, Peng A, Najjar R, Sethi S, Williamson S, Myers C, Lim K, Choi J, Vo A. Clazakizumab (Anti-IL-6) Induces Foxp3+ Tregs in Highly HLA Sensitized Patients Desensitized for HLAi Transplantation (NCT03380962) [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/clazakizumab-anti-il-6-induces-foxp3-tregs-in-highly-hla-sensitized-patients-desensitized-for-hlai-transplantation-nct03380962/. Accessed June 15, 2021.
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