Genetics of natural resistance to herpesvirus infections in mice

López, Carlos

doi:10.1038/258152a0

Cited by 336 publications

(223 citation statements)

References 15 publications

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“…We used two genetically distinct strains of mice, A/J and BALB/c, with differing sensitivity to HSV infection, 27 to account for possible genetic variability in the immune response. Both strains of mice produced similar levels of anti-HSV antibodies after i.p.…”

Section: Figure 3 Elisa For Hsv Antibodies In Serum Of Tumor-bearing mentioning

confidence: 99%

“…The A/J mice received a smaller dose of HSV-1 than the BALB/c mice due to their lower LD 50 . 24,27 The control groups (n = 13) were injected similarly with saline.…”

Section: Hsv Exposurementioning

confidence: 99%

“…A/J is more susceptible to lethal HSV infection than BALB/c. 27 For these studies, we used two subcutaneous tumor models, CT26, a colorectal tumor cell line syngeneic to BALB/c mice that is poorly immunogenic, 28,29 and N18, a neuroblastoma tumor cell line syngeneic to A/J mice that is moderately immunogenic (Todo T, unpublished data). N18 cells are moderately sensitive to G207-mediated cell death and replication in vitro (Todo T, unpublished data), whereas, CT26 cells are less sensitive.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1999

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Replication-competent, attenuated mutants of herpes simrespectively. Established tumors were subsequently plex virus type 1 (HSV-1) have been shown to be effitreated intratumorally with a multi-mutated HSV-1, G207. cacious for tumor therapy. However, these studies did not G207 inhibited tumor growth to a similar extent whether address the consequences of prior exposure to HSV, as the mice were seropositive or not. We next examined the will be the case with many patients likely to receive this effect of multiple intratumoral inoculations of a 10-fold therapy. Two strains of mice, A/J and BALB/c, were lower dose of G207 on tumor growth. In the multiple treatinfected with wild-type HSV-1 by intraperitoneal injection ment group (biweekly for 3 weeks), 75% of tumors were and the immune response was determined by plaque cured, whereas no cures were seen in the single treatment reduction assay for neutralizing antibody and ELISA for group. We conclude that HSV seropositivity should not delIgG and IgM. Syngeneic tumors, N18 neuroblastoma and eteriously affect the efficacy of G207 tumor therapy, and CT26 colon carcinoma, were implanted subcutaneously in multiple inoculations of virus should be considered for HSV-1 seropositive and naive A/J and BALB/c mice, clinical evaluation.

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Section: Figure 3 Elisa For Hsv Antibodies In Serum Of Tumor-bearing mentioning

confidence: 99%

“…The A/J mice received a smaller dose of HSV-1 than the BALB/c mice due to their lower LD 50 . 24,27 The control groups (n = 13) were injected similarly with saline.…”

Section: Hsv Exposurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 1999

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“…BALB/c mice were chosen because they are known to be susceptible to HSV infection. 18 None of R-LM113 intracranially inoculated BALB/c mice developed fatal inflammation nor showed signs of infection (EGFP expression), demonstrating that R-LM113 did not elicit a dangerous immune response and therefore it is safe also in an immunocompetent animal.…”

Section: Discussionmentioning

confidence: 93%

“…As mouse strains significantly diverge in their susceptibility to viral infections, we selected the BALB/c mouse strain, which is known to be susceptible to HSV. 17,18 In this study, we provided evidence that both the safety and the therapeutic efficacy of the replication-competent HSV R-LM113 are not spoiled by the immune system.…”

Section: Introductionmentioning

confidence: 84%

Efficacy of HER2 retargeted herpes simplex virus as therapy for high-grade glioma in immunocompetent mice

et al. 2012

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Replication-competent oncolytic herpes simplex viruses (HSVs) are considered a promising therapeutic approach for treatment of high-grade gliomas (HGGs), which are usually resistant to all the available treatments. We previously demonstrated that R-LM113, a recombinant HSV-1 fully retargeted to the human epidermal growth factor receptor 2 (HER2), is safe and prolongs survival of immunodeficient NOD/SCID mice in an intracranial model of HGG. However, because the treatment is designed to be employed on immunocompetent patients, it is necessary to test whether the host immune system impairs the viral efficacy or triggers a potentially fatal reaction. Here we confirmed the safety of R-LM113 in the immunocompetent mouse strain BALB/c, where it does not trigger encephalitis when intracranially inoculated. Then, we set up a syngeneic HGG model expressing HER2 in adult BALB/c mice and evaluated R-LM113 therapeutic efficacy. We found that R-LM113 leads to a significant improvement in animal survival when administered at the time of tumor inoculation, as well as when injected into an already established tumor. This study suggests that the host immune defenses do not curtail the oncolytic antitumor activity of replication-competent HSV R-LM113, which results effective in counteracting tumor growth.

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