Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein.

Animals Antibodies, Monoclonal / pharmacology Antibody-Dependent Cell Cytotoxicity / immunology Brucella / enzymology Female Histocompatibility Antigens Class I / genetics Lymphoma / immunology Male Mice Mice, Inbred C57BL Multienzyme Complexes / genetics NK Cell Lectin-Like Receptor Subfamily K / genetics Recombinant Fusion Proteins / immunology Tumor Cells, Cultured Urinary Bladder Neoplasms / immunology

immunology

Journal

Journal for immunotherapy of cancer

ISSN: 2051-1426

Titre abrégé: J Immunother Cancer

Pays: England

ID NLM: 101620585

Informations de publication

Date de publication:
06 2020

Historique:

accepted: 05 03 2020

entrez: 11 6 2020

pubmed: 11 6 2020

medline: 17 3 2021

Statut: ppublish

Résumé

Natural killer and cytotoxic CD8 We generated a highly immunogenic chimeric protein (BLS-MICA) consisting of human MICA fused to the lumazine synthase from Immunization with BLS-MICA and administration of anti-MICA pAb elicited by BLS-MICA significantly delayed the growth of MICA-expressing mouse tumors but not of control tumors. The therapeutic effect of immunization with BLS-MICA included scavenging of sMICA and the anti-MICA Ab-mediated ADCC, promoting heightened intratumoral M1/proinflammatory macrophage and antigen-experienced CD8 Immunization with the chimeric protein BLS-MICA constitutes a useful way to actively induce therapeutic anti-MICA pAb that resulted in a reprogramming of the antitumor immune response towards an antitumoral/proinflammatory phenotype. Hence, the BLS-MICA chimeric protein constitutes a novel antitumor vaccine of potential application in patients with MICA-expressing tumors.

Sections du résumé

BACKGROUND

Natural killer and cytotoxic CD8

METHODS

We generated a highly immunogenic chimeric protein (BLS-MICA) consisting of human MICA fused to the lumazine synthase from

RESULTS

Immunization with BLS-MICA and administration of anti-MICA pAb elicited by BLS-MICA significantly delayed the growth of MICA-expressing mouse tumors but not of control tumors. The therapeutic effect of immunization with BLS-MICA included scavenging of sMICA and the anti-MICA Ab-mediated ADCC, promoting heightened intratumoral M1/proinflammatory macrophage and antigen-experienced CD8

CONCLUSIONS

Immunization with the chimeric protein BLS-MICA constitutes a useful way to actively induce therapeutic anti-MICA pAb that resulted in a reprogramming of the antitumor immune response towards an antitumoral/proinflammatory phenotype. Hence, the BLS-MICA chimeric protein constitutes a novel antitumor vaccine of potential application in patients with MICA-expressing tumors.

Identifiants

DOI: 10.1136/jitc-2019-000233 PMID: 32518090 PMC: PMC7282397

pubmed: 32518090

pii: jitc-2019-000233

doi: 10.1136/jitc-2019-000233

pmc: PMC7282397

pii:

doi:

Substances chimiques

Antibodies, Monoclonal 0

Histocompatibility Antigens Class I 0

MHC class I-related chain A 0

Multienzyme Complexes 0

NK Cell Lectin-Like Receptor Subfamily K 0

Recombinant Fusion Proteins 0

6,7-dimethyl-8-ribityllumazine synthase 89287-46-7

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Informations de copyright

Déclaration de conflit d'intérêts

Competing interests: None declared.

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