RRC ID 44034
Author Esaki S, Goshima F, Kimura H, Murakami S, Nishiyama Y.
Title Enhanced antitumoral activity of oncolytic herpes simplex virus with gemcitabine using colorectal tumor models.
Journal Int J Cancer
Abstract To enhance the oncolytic activity of herpes simplex viruses (HSVs) control of immune-suppression and immune-resistance by cancer cells is important. Myeloid-derived suppressor cells (MDSCs), which interfere with tumor-suppressive environments, are inhibited by gemcitabine (GEM) treatment. We investigated the oncolytic activity and systemic antitumor immunity induced by oncolytic HSVs in combination with GEM treatment. A mouse model with subcutaneous tumors on both sides of the lateral flanks was used. A highly attenuated HSV type 1, strain HF10, was inoculated into one side of each tumor three times following intraperitoneal injection of GEM. Histopathological changes and IFN-γ secretion of the tumor and leukocytes in the spleen were analyzed. These treatments were repeated to enhance oncolytic activity. HF10 inoculation reduced tumor growth only on the HF10-treated side. HF10 inoculation following GEM treatment resulted in greater reduction of tumor growth on the HF10-treated tumor; furthermore, reduction of tumors on the contralateral untreated side was also observed. Necrosis of the tumor was observed in areas where HSV-infected cells were detected. F4/80(+) macrophages around the tumor were eliminated, and CD4(+) T and CD8(+) T cells increased in the spleen. A single injection of GEM decreased CD11b(+) /Gr-1(+) MDSCs while retaining CD4(+) T cells and CD8(+) T cells. Repetition of this treatment regimen resulted in even greater reduction of tumor growth on both sides and complete rejection in some of the mice. Intratumoral injection of oncolytic HSVs following GEM injection reduced MDSCs. Repeated treatment with oncolytic HSVs following GEM resulted in enhanced oncolytic activity.
Volume 132(7)
Pages 1592-601
Published 2013-4-1
DOI 10.1002/ijc.27823
PMID 22949155
MeSH Animals Antigen Presentation Antimetabolites, Antineoplastic / therapeutic use* Chlorocebus aethiops Colorectal Neoplasms / immunology Colorectal Neoplasms / pathology Colorectal Neoplasms / therapy* Combined Modality Therapy Deoxycytidine / analogs & derivatives* Deoxycytidine / therapeutic use Disease Models, Animal* Female Herpes Simplex / immunology* Herpes Simplex / metabolism Herpes Simplex / virology Injections, Intralesional Interferon-gamma / metabolism Mice Mice, Inbred BALB C Oncolytic Virotherapy* Simplexvirus / physiology* Spleen / drug effects Spleen / immunology Spleen / pathology T-Lymphocytes / drug effects T-Lymphocytes / immunology T-Lymphocytes / virology Vero Cells
IF 5.145
Times Cited 22
Human and Animal Cells Vero(RCB0001)