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Combining oncolytic HSV-1 with immunogenic cell death-inducing drug mitoxantrone breaks cancer immune tolerance and improves therapeutic efficacy.
- Source :
-
Cancer immunology research [Cancer Immunol Res] 2013 Nov; Vol. 1 (5), pp. 309-19. Date of Electronic Publication: 2013 Aug 19. - Publication Year :
- 2013
-
Abstract
- Although antitumor activity of herpes simplex virus 1 (HSV-1) ICP0 null oncolytic vectors has been validated in murine breast cancer models, oncolytic virus treatment alone is insufficient to break immune tolerance. Thus, we investigated enhancing efficacy through combination therapy with the immunogenic cell death-inducing chemotherapeutic drug, mitoxantrone. Despite a lack of enhanced cytotoxicity in vitro, HSV-1 ICP0 null oncolytic virus KM100 with 5 μmol/L mitoxantrone provided significant survival benefit to BALB/c mice bearing Her2/neu TUBO-derived tumors. This protection was mediated by increased intratumoral infiltration of neutrophils and tumor antigen-specific CD8(+) T cells. Depletion studies verified that CD8-, CD4-, and Ly6G-expressing cells are essential for enhanced efficacy of the combination therapy. Moreover, the addition of mitoxantrone to KM100 oncolytic virus treatment broke immune tolerance in BALB-neuT mice bearing TUBO-derived tumors. This study suggests that oncolytic viruses in combination with immunogenic cell death-inducing chemotherapeutics enhance the immunogenicity of the tumor-associated antigens, breaking immunologic tolerance established toward these antigens.<br /> (©2013 AACR.)
- Subjects :
- Animals
Bone Neoplasms drug therapy
Bone Neoplasms immunology
Bone Neoplasms pathology
CD8-Positive T-Lymphocytes immunology
Cell Death drug effects
Cell Line, Tumor
Combined Modality Therapy
Humans
Immune Tolerance
Mice
Mice, Inbred BALB C
Mice, Transgenic
Osteosarcoma drug therapy
Osteosarcoma immunology
Osteosarcoma pathology
Receptor, ErbB-2 immunology
Antineoplastic Agents pharmacology
Bone Neoplasms therapy
Herpesvirus 1, Human physiology
Mitoxantrone pharmacology
Oncolytic Virotherapy methods
Oncolytic Viruses physiology
Osteosarcoma therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2326-6074
- Volume :
- 1
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cancer immunology research
- Publication Type :
- Academic Journal
- Accession number :
- 24777969
- Full Text :
- https://doi.org/10.1158/2326-6066.CIR-13-0059-T