Synergistic Efficacy of an Interleukin 2 Analog and Antitumor Antigen Antibody

主要研究者/项目负责人（末、中、首：陈日东 摘要 白细胞介素-2（IL-2）免疫治疗可通过以下方式在某些癌症患者中产生显著的长期应答： 刺激免疫反应杀死肿瘤细胞。然而，目前的rIL-2治疗仅限于高度选择的 由于其需要高剂量和频繁给药，这可能导致严重的副作用。此外，委员会认为， rIL-2还激活抑制免疫应答的CD 4+调节性T细胞。减轻债务 在目前的rIL-2药物中，我们设计了一种长效IL-2类似物，可选择性地保留免疫应答 活化（CD 8 + T，NK细胞），而不活化调节性T细胞和内皮细胞;从而， 免疫抑制和血管渗漏综合征。我们建议优化rIL 2类似物治疗的组合， 加上抗肿瘤抗体，通过协同的先天性和适应性反应安全有效地杀死肿瘤细胞 涉及中性粒细胞、NK细胞、巨噬细胞和CD 8 + T细胞。 本研究的具体目的是利用B16-F10的同基因小鼠模型， 专有的IL-2类似物与抗肿瘤抗原抗体的组合有效地根除了已建立的 而不会引起不良副作用。我们的长期目标是开发专有的IL-2类似物， 安全的免疫疗法来治愈癌症或延长患者的生存期。

Principal Investigator/Program Director (Last, First, Middle: Chen, Ridong Abstract Interleukin-2 (IL-2) immunotherapy can result in remarkable long-term responses in some cancer patients by stimulating the immune response to kill tumor cells. However, current rIL-2 therapy is limited to highly selected patients due to its requirements for high and frequent dosing, which can result in severe side effects. Moreover, rIL-2 also activates CD4+ regulatory T cells, which suppress the immune response. To ameliorate the liabilities of the current rIL-2 drug, we have designed a long-acting IL-2 analog that selectively preserves immune response activation (CD8+ T, NK cells), without activating regulatory T cells and endothelial cells; thereby, minimizing immune suppression and vascular leak syndrome. We propose to optimize combination of rIL2 analog treatment plus antitumor antibody to safely and effectively kill tumor cells via a concerted innate and adaptive response involving neutrophils, NK cells, macrophages, and CD8+ T cells. In this study, the Specific Aim is to use the syngeneic mouse model of B16-F10 to determine whether the combination of the proprietary IL-2 analog with an antitumor antigen antibody effectively eradicates established tumors without inducing adverse side effects. Our long-term goal is to develop the proprietary IL-2 analog as a safe immunotherapy to cure cancer or extend survival of patients.