Greiner John W, Morillon Y Maurice, Schlom Jeffrey
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Immunotargets Ther. 2021 May 27;10:155-169. doi: 10.2147/ITT.S306150. eCollection 2021.
NHS-IL12 is a novel immunocytokine designed for delivery of IL-12 to the tumor microenvironment (TME). NHS-IL12 consists of two molecules of IL-12 fused to a human IgG1 (NHS76) recognizing DNA/histone complexes, which are often exposed in the necrotic portions of tumors. Preclinical studies demonstrated the tumor-targeting ability and longer plasma half-life for NHS-IL12 when compared with recombinant IL-12 (rIL-12). NHS-IL12 outperformed rIL-12 in enhancing the proliferation and activation of immune as well as antigen-presenting cells, resulting in a more robust primary immune response. NHS-IL12 also reduced the number and function of suppressive myeloid cells (myeloid derived suppressor cells/macrophages) within the TME. In a murine bladder tumor model, NHS-IL12 administration led to a coordinated increase in host immunity with a reduction of immunosuppressive myeloid cells in the TME resulting in substantial reduction in tumor growth. Several preclinical studies have demonstrated increased overall anti-tumor efficacy when NHS-IL12 was combined with either immune-based therapeutics or chemotherapeutic approaches.
NHS-IL12是一种新型免疫细胞因子，旨在将白细胞介素-12（IL-12）递送至肿瘤微环境（TME）。NHS-IL12由两个与识别DNA/组蛋白复合物的人IgG1（NHS76）融合的IL-12分子组成，这些复合物常在肿瘤坏死部分暴露。临床前研究表明，与重组IL-12（rIL-12）相比，NHS-IL12具有肿瘤靶向能力且血浆半衰期更长。在增强免疫细胞和抗原呈递细胞的增殖与活化方面，NHS-IL12优于rIL-12，从而产生更强有力的初次免疫反应。NHS-IL12还减少了TME内抑制性髓系细胞（髓系来源的抑制细胞/巨噬细胞）的数量和功能。在小鼠膀胱肿瘤模型中，给予NHS-IL12导致宿主免疫力协同增强，TME中免疫抑制性髓系细胞减少，肿瘤生长显著降低。多项临床前研究表明，当NHS-IL12与基于免疫的治疗方法或化疗方法联合使用时，总体抗肿瘤疗效会提高。
