Article ; Online: Lactate oxidase nanocapsules boost T cell immunity and efficacy of cancer immunotherapy.
Science translational medicine
2023 Volume 15, Issue 717, Page(s) eadd2712
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 ... ...
| 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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| MeSH term(s) | Animals ; Mice ; T-Lymphocytes ; Nanocapsules ; Immunotherapy ; Melanoma/therapy ; Lactates ; Tumor Microenvironment |
| Chemical Substances | Nanocapsules ; lactate 2-monooxygenase (EC 1.13.12.4) ; Lactates |
| Language | English |
| Publishing date | 2023-10-11 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2518854-9 |
| ISSN | 1946-6242 ; 1946-6234 |
| ISSN (online) | 1946-6242 |
| ISSN | 1946-6234 |
| DOI | 10.1126/scitranslmed.add2712 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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