Multifunctional Enzyme Nanocapsules Boost T Cell Immunity and Multifunctional Enzyme Nanocapsules Boost T Cell Immunity and Efficacy of Cancer Immunotherapy

Cancer immunotherapy has reshaped the landscape of cancer treatment, but its effectiveness is limited by tumor immunosuppression caused by excessive lactate production by cancer cells. While efforts to reduce lactate levels through lactate dehydrogenase inhibition have been made, such inhibitors can disrupt the metabolism of healthy cells and cause severe non-specific toxicity. Based on lactate oxidase, we report herein an enzyme therapeutic, which reduces lactate levels, releases an immunostimulatory molecule-hydrogen peroxide, averts tumor immunosuppression, and synergistically improves the efficacy of immune checkpoint blockades, as demonstrated in a murine melanoma model and a humanized mouse model of triple-negative breast cancer. Single-cell RNA seq of tumor cells treated with and without nanoparticles

癌症免疫疗法（cancer immunotherapy）重塑了癌症治疗的整体格局，但其疗效却受到癌细胞过度合成乳酸（lactate）所介导的肿瘤免疫抑制（tumor immunosuppression）的限制。尽管已有研究尝试通过抑制乳酸脱氢酶（lactate dehydrogenase）来降低乳酸水平，但这类抑制剂会干扰健康细胞的代谢进程，并引发严重的非特异性毒性。本研究基于乳酸氧化酶（lactate oxidase）开发了一款酶类治疗剂，该制剂可降低乳酸水平、释放免疫刺激分子——过氧化氢（hydrogen peroxide）、逆转肿瘤免疫抑制，并协同增强免疫检查点阻断剂（immune checkpoint blockades）的治疗效果，相关疗效在小鼠黑色素瘤模型（murine melanoma model）与三阴性乳腺癌（triple-negative breast cancer）人源化小鼠模型（humanized mouse model）中得到验证。本数据集涵盖经纳米颗粒（nanoparticles）处理与未处理的肿瘤细胞的单细胞RNA测序（single-cell RNA seq）结果。