A vaccine targeting resistant tumours by dual T cell plus NK cell attack.

Autor: Badrinath S; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Immunology, Harvard Medical School, Boston, MA, USA., Dellacherie MO; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Li A; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.; Lyell Immunopharma, South San Francisco, CA, USA., Zheng S; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Genetics and Genomic Sciences, Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Zhang X; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Immunology, Harvard Medical School, Boston, MA, USA., Sobral M; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Pyrdol JW; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA., Smith KL; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA., Lu Y; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA., Haag S; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Immunology, Harvard Medical School, Boston, MA, USA., Ijaz H; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Connor-Stroud F; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA., Kaisho T; Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan., Dranoff G; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Novartis Institutes for BioMedical Research, Cambridge, MA, USA., Yuan GC; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Genetics and Genomic Sciences, Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Mooney DJ; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Wucherpfennig KW; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. Kai_Wucherpfennig@dfci.harvard.edu.; Department of Immunology, Harvard Medical School, Boston, MA, USA. Kai_Wucherpfennig@dfci.harvard.edu.; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA. Kai_Wucherpfennig@dfci.harvard.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Jun; Vol. 606 (7916), pp. 992-998. Date of Electronic Publication: 2022 May 25.
DOI: 10.1038/s41586-022-04772-4
Abstrakt: Most cancer vaccines target peptide antigens, necessitating personalization owing to the vast inter-individual diversity in major histocompatibility complex (MHC) molecules that present peptides to T cells. Furthermore, tumours frequently escape T cell-mediated immunity through mechanisms that interfere with peptide presentation 1 . Here we report a cancer vaccine that induces a coordinated attack by diverse T cell and natural killer (NK) cell populations. The vaccine targets the MICA and MICB (MICA/B) stress proteins expressed by many human cancers as a result of DNA damage 2 . MICA/B serve as ligands for the activating NKG2D receptor on T cells and NK cells, but tumours evade immune recognition by proteolytic MICA/B cleavage 3,4 . Vaccine-induced antibodies increase the density of MICA/B proteins on the surface of tumour cells by inhibiting proteolytic shedding, enhance presentation of tumour antigens by dendritic cells to T cells and augment the cytotoxic function of NK cells. Notably, this vaccine maintains efficacy against MHC class I-deficient tumours resistant to cytotoxic T cells through the coordinated action of NK cells and CD4 + T cells. The vaccine is also efficacious in a clinically important setting: immunization following surgical removal of primary, highly metastatic tumours inhibits the later outgrowth of metastases. This vaccine design enables protective immunity even against tumours with common escape mutations.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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