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Lactate oxidase nanocapsules boost T cell immunity and efficacy of cancer immunotherapy.
Cao, Zheng; Xu, Duo; Harding, Jeffrey; Chen, Wenting; Liu, Xiangsheng; Wang, Zi; Wang, Lan; Qi, Tong; Chen, Shilin; Guo, Xinheng; Chen, Irvin S Y; Guo, Jimin; Lu, Yunfeng; Wen, Jing.
Afiliação
  • Cao Z; Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Xu D; UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Harding J; Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Chen W; UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Liu X; Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
  • Wang Z; Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Wang L; Division of Nanomedicine, Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Qi T; Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Chen S; UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Guo X; Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
  • Chen ISY; UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Guo J; Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
  • Lu Y; Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Wen J; Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA 90095, USA.
Sci Transl Med ; 15(717): eadd2712, 2023 10 11.
Article em En | MEDLINE | ID: mdl-37820006
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nanocápsulas / Melanoma Limite: Animals Idioma: En Revista: Sci Transl Med Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nanocápsulas / Melanoma Limite: Animals Idioma: En Revista: Sci Transl Med Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos