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Oncolytic Herpes Virus G47Δ Potentiates ADCC-Inducing Molecular Targeted Therapy via Coordinated Activation of Innate and Adaptive Immune Responses.

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Τίτλος: Oncolytic Herpes Virus G47Δ Potentiates ADCC-Inducing Molecular Targeted Therapy via Coordinated Activation of Innate and Adaptive Immune Responses.
Συγγραφείς: Nagatomo T; Division of Innovative Cancer Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.; Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University, Tochigi-ken, Japan., Iwai M; Division of Innovative Cancer Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Tanaka M; Division of Innovative Cancer Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Nishino H; Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University, Tochigi-ken, Japan., Todo T; Division of Innovative Cancer Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Πηγή: Molecular cancer therapeutics [Mol Cancer Ther] 2026 Oct 02; Vol. 25 (10), pp. 1691-1701.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: American Association for Cancer Research, Inc Country of Publication: United States NLM ID: 101132535 Publication Model: Print Cited Medium: Internet ISSN: 1538-8514 (Electronic) Linking ISSN: 15357163 NLM ISO Abbreviation: Mol Cancer Ther Subsets: MEDLINE
Imprint Name(s): Original Publication: Philadelphia, PA : American Association for Cancer Research, Inc., c2001-
Ιατρικοί όροι (MeSH): Oncolytic Virotherapy*/methods , Oncolytic Viruses*/genetics , Oncolytic Viruses*/immunology , Antibody-Dependent Cell Cytotoxicity*/immunology , Antibody-Dependent Cell Cytotoxicity*/drug effects , Immunity, Innate* , Adaptive Immunity*, Cetuximab/pharmacology ; ErbB Receptors/antagonists & inhibitors ; Dendritic Cells/immunology ; Killer Cells, Natural/immunology ; Animals ; Humans ; Mice ; Cell Line, Tumor ; Molecular Targeted Therapy ; Female ; Disease Models, Animal
Περίληψη: Antibody-dependent cellular cytotoxicity (ADCC) is a key player in the antitumor immunity elicited through molecular targeted therapy of oncogenic receptors using monoclonal antibodies (mAb). Oncolytic viruses represent an alternative therapeutic means that selectively replicate in and destroy tumor cells, as well as induce specific antitumor immune responses. This study investigates whether oncolytic virus therapy using G47Δ, a third-generation oncolytic herpes virus with enhanced induction of antitumor immunity, can augment the efficacy of molecular targeted therapy with ADCC using the anti-epidermal growth factor receptor (EGFR) mAb cetuximab. Due to the species specificity of cetuximab, we developed a human EGFR-expressing immunocompetent murine tumor model specific to the ADCC activity of cetuximab. Intratumoral G47Δ administration combined with systemic cetuximab treatment was significantly more effective in suppressing tumor growth than G47Δ monotherapy. This phenomenon was dependent upon the activation of both innate and adaptive immune cells, as antitumor responses were abrogated upon natural killer cell and CD8+ T-cell depletion. Further studies investigating the draining lymph node dendritic cells (DC) indicate that the destruction of cetuximab-coated tumor cells by G47Δ promotes uptake of tumor cells by DCs, enhances the priming of immune responses, and subsequently stimulates tumor-specific CD8+ T cells. These results suggest that the combination of G47Δ therapy and molecular targeted therapies with ADCC activity may represent a useful therapeutic strategy for enhancing antitumor immune responses, even after the emergence of acquired resistance.
(©2026 The Authors; Published by the American Association for Cancer Research.)
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Grant Information: JP17lm0203004 Japan Agency for Medical Research and Development (AMED); JP20lm0203140 Japan Agency for Medical Research and Development (AMED); Japan Agency for Medical Research and Development (AMED); JP18ck0106416 Japan Agency for Medical Research and Development (AMED)
Substance Nomenclature: PQX0D8J21J (Cetuximab)
EC 2.7.10.1 (ErbB Receptors)
Entry Date(s): Date Created: 20260505 Date Completed: 20261002 Latest Revision: 20261004
Update Code: 20261004
PubMed Central ID: PMC13631497
DOI: 10.1158/1535-7163.MCT-25-1350
PMID: 42085638
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1538-8514
DOI:10.1158/1535-7163.MCT-25-1350