Abstract 1842: The safety assessment and the pharmacodynamics evaluation of therapeutic cytokine in non-human primates

Abstract

Abstract Cytokines are indispensable regulators of innate and adaptive immunity that transfer signals between cells over short distances. Given their abilities to initiate and activate immune responses, cytokines have long been utilized in cancer therapy, whereas there are limitations, short half-life, pleiotropism, functional redundancy, and side effects, slow down the wide application of cytokine therapy. Thus, evaluating the pharmaceutical properties of cytokines or their translated forms, such as supercytokines, immunocytokines, engager cytokines, and synthetic cytokines, in non-human primates shall be a substantial approach to guide and define clinical trial strategies of cytokine-based therapies. In this study, Interleukin-15 (IL-15) is preferably focused due to its potential in proliferating natural killer cells and cytotoxic T lymphocytes by which host’s immunity was boosted to fight against tumor progression. To evaluate the safety and pharmacodynamics of IL-15 in vivo, rhesus macaques were administered intravenously with recombinant human IL-15 (rhIL-15). We revealed that intravenous administration of rhIL-15 to rhesus macaques caused a slightly weight loss and neutropenia, while no other abnormalities were observed during the whole study. Moreover, the level of C-reactive protein (CRP) was found significantly elevated which was consistent with the increased abundance of MCP1, CCL4, and IL-RA chemokines in serum, suggesting that IL-15 treatment induces acute inflammatory response. Furthermore, flow cytometry analysis showed the activation, proliferation and expansion of memory T and NK cells after receiving IL-15. In conclusion, our study deepens the understanding of T and NK cell homeostasis after IL-15 administration in NHPs and may offer critical clinical strategies for human trials. Citation Format: Wei Li, Yixuan Xu, Xin Zhou, Dan Zhu, Meng Xiao, Yulin Zhou, Zhijie Yang, Haodong Li, Bo Pang, Xinghai Song, Yan Xiao, Wenting Shi, Qian Qian, Qingyang Gu. The safety assessment and the pharmacodynamics evaluation of therapeutic cytokine in non-human primates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1842.