Zhu Eric F, Gai Shuning A, Opel Cary F, Kwan Byron H, Surana Rishi, Mihm Martin C, Kauke Monique J, Moynihan Kelly D, Angelini Alessandro, Williams Robert T, Stephan Matthias T, Kim Jacob S, Yaffe Michael B, Irvine Darrell J, Weiner Louis M, Dranoff Glenn, Wittrup K Dane
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cancer Cell. 2015 Apr 13;27(4):489-501. doi: 10.1016/j.ccell.2015.03.004.
Cancer immunotherapies under development have generally focused on either stimulating T cell immunity or driving antibody-directed effector functions of the innate immune system such as antibody-dependent cell-mediated cytotoxicity (ADCC). We find that a combination of an anti-tumor antigen antibody and an untargeted IL-2 fusion protein with delayed systemic clearance induces significant tumor control in aggressive isogenic tumor models via a concerted innate and adaptive response involving neutrophils, NK cells, macrophages, and CD8(+) T cells. This combination therapy induces an intratumoral "cytokine storm" and extensive lymphocyte infiltration. Adoptive transfer of anti-tumor T cells together with this combination therapy leads to robust cures of established tumors and development of immunological memory.
正在研发的癌症免疫疗法通常要么专注于刺激T细胞免疫，要么驱动先天免疫系统的抗体导向效应功能，如抗体依赖性细胞介导的细胞毒性（ADCC）。我们发现，一种抗肿瘤抗原抗体与一种具有延迟全身清除功能的非靶向IL-2融合蛋白的组合，通过涉及中性粒细胞、自然杀伤细胞、巨噬细胞和CD8(+) T细胞的协同先天和适应性反应，在侵袭性同基因肿瘤模型中诱导显著的肿瘤控制。这种联合疗法诱导肿瘤内“细胞因子风暴”和广泛的淋巴细胞浸润。将抗肿瘤T细胞与这种联合疗法一起进行过继性转移可实现对已建立肿瘤的强力治愈并产生免疫记忆。
