Effect of prior exposure to herpes simplex virus 1 on viral vector-mediated tumor therapy in immunocompetent mice

Chahlavi, Ali; Rabkin, Samuel D.; Todo, Tomoki; Sundaresan, Periasamy; Martuza, Robert L.

doi:10.1038/sj.gt.3301003

Cited by 93 publications

(57 citation statements)

References 49 publications

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“…This demonstrated that tumours were effectively treated even following prior immunization with HSV, there being no detectable difference in the magnitude of the anti-tumour effect as compared to the previous experiments reported above ( Figure 9). Thus, as previously reported for a previous version of oncolytic HSV, 38 prior immunity to HSV does not have a significant effect on the ability of the virus to treat tumours.…”

Section: Pre-existing Anti-hsv Immunity Does Not Affect the Anti-tumosupporting

confidence: 80%

See 1 more Smart Citation

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties

Liu¹,

Robinson²,

Han³

et al. 2003

Gene Ther

709

624

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Section: Pre-existing Anti-hsv Immunity Does Not Affect the Anti-tumosupporting

confidence: 80%

“…38 Balb/c mice were immunized i.p. with 5 Â 10 3 pfu wild-type HSV1 (17+) in PBS 5 weeks before tumour induction.…”

Section: Prior Immunization Of Micementioning

confidence: 99%

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties

Liu¹,

Robinson²,

Han³

et al. 2003

Gene Ther

709

624

View full text Add to dashboard Cite

“…Neither antibody nor cellular proliferative responses elicited in mice immunized with a replication-defective HSV vector were affected by prior exposure to HSV [38]. Additionally, treatment of tumor-bearing mice with oncolytic HSV was not adversely effected even in mice with prior HSV-1 immunity [36]. Other studies in mice seropositive for HSV-1 have indicated that humoral and cell-mediated immune responses are significantly reduced following immunization with replication-defective HSV vectors as compared to immunization of HSV-1 naïve mice [69].…”

Section: Discussionmentioning

confidence: 92%

“…Herpes simplex virus type-1 (HSV-1) with deletions in the Δγ 1 34.5 gene is replication-competent but is aneurovirulent [23]. Attenuated HSV-1 recombinants are attractive as HIV-1 vaccine vectors for multiple reasons: i) herpesvirus vectors can infect dendritic cells and stimulate potent, longlasting CMI responses [24][25][26][27][28]; ii) attenuated HSV can establish latency and reactivate with the potential to prolong an immune response [29,30]; iii) several nonessential genes can be deleted and replaced with multiple foreign gene inserts (up to 30 kb) [31]; vi) HSV Δγ 1 34.5 viruses have been safe during human use in clinical trials, including intracranial injection at high doses [32][33][34][35]; and v) although prior immunity to HSV has a variable effect on vector efficacy in gene therapy applications, it does not impair either antibody or CMI responses elicited against immunogens expressed from HSV vectors [36][37][38][39].…”

Section: Introductionmentioning

confidence: 99%

HIV-189.6 Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in mice

Parker

Rottinghaus

Zajac

et al. 2007

Vaccine

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We have constructed a replication competent, γ 1 34.5-deleted Herpes Simplex Virus type 1 (HSV-1) vector (J200) that expresses the gag gene from Human Immunodeficiency Virus type-1, primary isolate 89.6 (HIV-1 89.6 ), as a candidate vaccine for HIV-1. J200 replicates in vitro, resulting in abundant Gag protein production and accumulation in the extracellular media. Immunization of Balb/ c mice with a single intraperitoneal injection of J200 elicited strong Gag-specific CD8 responses, as measured by intracellular IFN-γ staining and flow cytometry analysis. Responses were highest between 6 weeks and 4 months, but persisted at 9 months post-immunization, the last time-point evaluated. These data highlight the potential utility of neuroattenuated, replication-competent HSV-1 vectors for delivery of HIV-1 immunogens.

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“…49 We have recently used N18 murine neuroblastoma cells that are moderately susceptible to G207 and reproducibly form s.c. or intracerebral tumors in syngeneic A/J mice. 50,51 This immunocompetent mouse tumor model has proven suitable for testing of the therapeutic efficacy of recombinant HSV-1. In this study, we evaluate the effect of GCV on G207 tumor therapy in vitro using several different cell lines and in vivo using the N18 mouse tumor model.…”

mentioning

confidence: 99%

Evaluation of ganciclovir-mediated enhancement of the antitumoral effect in oncolytic, multimutated herpes simplex virus type 1 (G207) therapy of brain tumors

2000

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G207 is a multimutated, conditionally replicating herpes simplex virus type 1 (HSV-1) that retains an intact viral thymidine kinase (HSV-tk) gene. The virus exhibits oncolytic activity in various tumors and is being evaluated in patients with recurrent malignant glioma. In view of the potential for ganciclovir (GCV) to either enhance or inhibit the antitumoral activity of HSV-tk-retaining HSV-1 vectors, we evaluated the effect of GCV administration on the antitumoral activity of G207. In culture, addition of GCV either had no effect or inhibited the cytocidal action of G207 at replication-permissive temperatures, while it significantly increased the cell killing in three of the four cell lines studied when virus replication was inhibited at nonpermissive temperatures. Using a G207-permissive immunocompetent mouse tumor model, subcutaneous N18 neuroblastoma in syngeneic A/J mice, we found that GCV treatment did not affect G207-mediated tumor growth inhibition at a variety of viral doses (10 5 , 10 7 , and 10 7 ϫ 2 plaque-forming units). In A/J mice harboring intracerebral N18 tumors, GCV administration had no significant effect on the prolongation of survival by G207 inoculation. These findings suggest that GCV administration may not be beneficial to the efficacy of G207 tumor therapy under conditions that favor active viral replication, because the potential HSV-tk/GCV-mediated enhancement of G207 oncolytic activity may be balanced out by the inhibitory action of GCV on viral replication. Cancer Gene Therapy (2000) 7, 939 -946 Key words: Herpes simplex virus; viral therapy; ganciclovir; bystander effect; thymidine kinase; brain neoplasm.B rain tumors represent 9% of all primary tumors and are the second leading cause of death from neurological disease. 1,2 Gliomas account for 40 -67% of the primary brain tumors, and approximately three-fourths of gliomas are considered malignant. Secondary brain tumors due to metastatic malignancy are also common, and the frequency is increasing because of longer survival of cancer patients in general. Despite progress in microsurgical techniques and adjuvant chemotherapy and radiotherapy, little improvement has been noted in the survival rate of patients with malignant brain tumors. The use of herpes simplex virus thymidine kinase (HSVtk) gene transduction using replication-defective vectors followed by ganciclovir (GCV) administration is a therapeutic design that has been extensively studied in brain tumors. 3-14 GCV, a nucleoside analog, is phosphorylated by HSV-tk, but not by endogenous mammalian tk, and is further anabolized by cellular kinases to GCV triphosphate, which inhibits host cell DNA replication by chain termination. 15 An important, advantageous feature of this strategy is that surrounding nontransduced cells can be killed in the presence of GCV in addition to the cells transduced with HSV-tk gene. 3,7,16 In vitro studies have shown that this so-called bystander effect is associated with gap junctional intercellular communication, through which phosphorylated GCV...

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Effect of prior exposure to herpes simplex virus 1 on viral vector-mediated tumor therapy in immunocompetent mice

Cited by 93 publications

References 49 publications

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties

HIV-189.6 Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in mice

Evaluation of ganciclovir-mediated enhancement of the antitumoral effect in oncolytic, multimutated herpes simplex virus type 1 (G207) therapy of brain tumors

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