Immunotherapy with chimeric NKG2D receptors leads to long-term tumor-free survival and development of host antitumor immunity in murine ovarian cancer
Immunotherapy with chimeric NKG2D receptors leads to long-term tumor-free survival and development of host antitumor immunity in murine ovarian cancer
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DOI：
10.4049/jimmunol.180.1.72
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发表时间：
2008-01-01
影响因子：
4.4
通讯作者：
Sentman, Charles L.
中科院分区：
文献类型：
--
作者：
Barber, Amorette;Zhang, Tong;Sentman, Charles L.
卵巢癌是女性癌症死亡的主要原因之一，需要开发新的治疗方法来补充标准治疗方案，如化疗和放疗。在这项研究中，我们表明，用表达嵌合NKG 2D受体（chNKG 2D）的T细胞治疗能够使已建立卵巢肿瘤的小鼠长期无肿瘤生存。无肿瘤小鼠能够在原始肿瘤注射后225天拒绝卵巢肿瘤细胞的再激发。此外，chNKG 2D T细胞治疗诱导了对卵巢肿瘤细胞的特异性宿主免疫应答，包括CD 8（+）和CD 4（+）T细胞肿瘤特异性记忆应答的产生。chNKG 2D T细胞通过细胞毒性和嘌呤依赖性途径降低卵巢肿瘤负荷。具体来说，穿孔素、GM-CSF和IFN-γ的chNKG 2D T细胞表达对于完整的抗肿瘤功效至关重要。
Ovarian cancer is one of the leading causes of cancer death in women and the development of novel therapies is needed to complement the standard treatment options such as chemotherapy and radiation. In this study, we show that treatment with T cells expressing a chimeric NKG2D receptor (chNKG2D) was able to lead to long-term, tumor-free survival in mice bearing established ovarian tumors. Tumor-free mice were able to reject a rechallenge with ovarian tumor cells 225 days after original tumor injection. In addition, chNKG2D T cell treatment induced specific host immune responses to ovarian tumor cells, including the development of both CD8(+) and CD4(+) T cell tumor-specific memory responses. The chNKG2D T cells reduced the ovarian tumor burden using both cytotoxic and cytokine-dependent pathways. Specifically, chNKG2D T cell expression of perforin, GM-CSF, and IFN-gamma were essential for complete antitumor efficacy.