Lactate oxidase nanocapsules boost T cell immunity and efficacy of cancer immunotherapy

Zheng Cao(University of California, Los Angeles), Duo Xu(University of California, Los Angeles), Jeffrey N. Harding(University of California, Los Angeles), Wenting Chen(University of California, Los Angeles), Xiangsheng Liu(University of California, Los Angeles), Zi Wang(University of California, Los Angeles), Lan Wang(University of California, Los Angeles), Qi Tong(University of California, Los Angeles), Shilin Chen(University of California, Los Angeles), Xinheng Guo(University of California, Los Angeles), Irvin S. Y. Chen(University of California, Los Angeles), Jimin Guo(University of California, Los Angeles), Yunfeng Lu(University of California, Los Angeles), Jing Wen(University of California, Los Angeles)
Science Translational Medicine
October 11, 2023
10.1126/scitranslmed.add2712
Cited by 116Open Access
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Abstract

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.

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