乳酸氧化酶纳米胶囊可增强 T 细胞免疫力和癌症免疫治疗的功效。
Lactate oxidase nanocapsules boost T cell immunity and efficacy of cancer immunotherapy.
发表日期:2023 Oct 11
作者:
Zheng Cao, Duo Xu, Jeffrey Harding, Wenting Chen, Xiangsheng Liu, Zi Wang, Lan Wang, Tong Qi, Shilin Chen, Xinheng Guo, Irvin S Y Chen, Jimin Guo, Yunfeng Lu, Jing Wen
来源:
Science Translational Medicine
摘要:
癌症免疫疗法重塑了癌症治疗的格局。然而,其功效仍然受到与癌细胞过量产生乳酸相关的肿瘤免疫抑制的限制。尽管已经做出了大量努力通过抑制乳酸脱氢酶来降低乳酸浓度,但此类抑制剂会破坏健康细胞的新陈代谢,导致严重的非特异性毒性。我们在此报告了一种基于乳酸氧化酶的纳米胶囊酶治疗剂,它可以降低乳酸浓度并释放免疫刺激性过氧化氢,避免肿瘤免疫抑制并提高免疫检查点阻断治疗的功效。正如小鼠黑色素瘤模型和三阴性乳腺癌人源化小鼠模型所证明的那样,这种酶疗法为更有效的癌症免疫疗法提供了有效的工具。
Cancer immunotherapy has reshaped the landscape of cancer treatment. However, its efficacy is still limited by tumor immunosuppression associated with the excessive production of lactate by cancer cells. Although extensive efforts have been made to reduce lactate concentrations through inhibition of lactate dehydrogenase, such inhibitors disrupt the metabolism of healthy cells, causing severe nonspecific toxicity. We report herein a nanocapsule enzyme therapeutic based on lactate oxidase, which reduces lactate concentrations and releases immunostimulatory hydrogen peroxide, averting tumor immunosuppression and improving the efficacy of immune checkpoint blockade treatment. As demonstrated in a murine melanoma model and a humanized mouse model of triple-negative breast cancer, this enzyme therapeutic affords an effective tool toward more effective cancer immunotherapy.