Background: CD122 is the Β chain of the receptors for IL-2 and IL-15, two key cytokines implicated in transplant rejection. HuABC2 (humanized IgG1, kappa) is the first high affinity anti-CD122 antibody created with potent inhibitory activity against both IL-2 and IL-15 mediated signaling. In a preliminary PD/PK study in normal cynomolgus monkeys, HuABC2 was well tolerated at a single dose of either 1 or 10 mg/kg and exhibited a half life of 3-7 days. Treated animals exhibited a transient, reversible depression in the number of CD8+ and CD16+ cells that were CD122+, an indication of effective IL-15 blockade. Methods: We tested HuABC2 as a monotherapy for the ability to prolong survival times of NHP recipients of life-sustaining kidney allografts. Two (ABO matched, MLR SI > 3) non-captive bred cynomolgus monkey pairs underwent heterotopic kidney allotransplantation after bilateral native nephrectomy. Animals were treated with 5 mg/kg HuABC2 IV immediately prior to surgery, and on days 3, 7, 10, 14, 21, 28, 42, 56, and 70. Three additional monkeys underwent surgery and served as untreated controls. Results: The three untreated animals exhibited a mean survival time of 6 days (5,6,7). At 42 days post transplant, two of the four HuABC2 treated animals exhibited good health and normal kidney function. One of the treated animals displayed a serum creatinine of 2.6 mg/dl beginning on day 1, which ultimately progressed to 28.09 mg/dl on day 28, when it was sacrificed. The remaining animal exhibited serum creatinine <2 mg/dl until it rose to 15.64 mg/dl on day 42. Final survival times, organ histology, as well as hematologic, serum biochemistry, and lymphocyte subpopulation monitoring results will be presented. Conclusion: This is the first report of the efficacy of the mechanistically novel anti-CD122 humanized antibody HuABC2 used as the only treatment to substantially prolong the survival times of NHP recipients of kidney allografts. The unique target, immunosuppressive efficacy, and clinical tolerability of HuABC2 supports investing further efforts to develop this anti-CD122 antibody as a novel calcineurin inhibitor-sparing agent for prevention of transplant rejection.
Landolfi, N.: Stockholder, JN Biosciences. Tsurushita, N.: Employee, JN Biosciences, Stockholder, JN Biosciences. Tso, J.: Employee, JN Biosciences, Stockholder, JN Biosciences.
To cite this abstract in AMA style:Landolfi N, Ma A, Song L, Dun H, Hu Y, Chen H, Tsurushita N, Tso J. Monotherapy with HuABC2, a Novel Humanized Antibody Against CD122 (The IL-2/IL-15 Receptor β Chain), Prolongs the Survival Times of Non-Human Primate (NHP) Recipients of Life-Sustaining Renal Allografts [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/monotherapy-with-huabc2-a-novel-humanized-antibody-against-cd122-the-il-2il-15-receptor-chain-prolongs-the-survival-times-of-non-human-primate-nhp-recipients-of-life-sustaining-renal-all/. Accessed December 5, 2020.
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