Direct vaccination with tumor cells killed with ICP4-deficient HSVd120 elicits effective antitumor immunity

Benencia, Fabián; Courrèges, Marı́a C.; Conejo-Garcia, José R.; Mohammed-Hadley, Alisha; Coukos, George

doi:10.4161/cbt.5.7.2908

Cited by 19 publications

(12 citation statements)

References 46 publications

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“…A vaccine composed of a nonreplicating HSV infected tumor that is irradiated and then presented to dendritic cells has been shown to produce a strong T cell response including the stimulation of tumor reactive IFN- γ secreting T cells and tumor reactive cytotoxic T cells [25]. IL-12 boosts the Th1 immune response and stimulates the production of IFN- γ and TNF- α .…”

Section: Discussionmentioning

confidence: 99%

Effect of HSV-IL12 Loaded Tumor Cell-Based Vaccination in a Mouse Model of High-Grade Neuroblastoma

Bauer

Pereboeva

Gillespie

et al. 2016

Journal of Immunology Research

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We designed multimodal tumor vaccine that consists of irradiated tumor cells infected with the oncolytic IL-12-expressing HSV-1 virus, M002. This vaccine was tested against the syngeneic neuroblastoma mouse model Neuro 2a injected into the right caudate nucleus of the immunocompetent A/J mice. Mice were vaccinated via intramuscular injection of multimodal vaccine or uninfected irradiated tumor cells at seven and 14 days after tumor establishment. While there was no survival difference between groups vaccinated with cell-based vaccine applied following tumor injection, a premunition prime/boost vaccination strategy produced a significant survival advantage in both groups and sustained immune response to an intracranial rechallenge of the same tumor. The syngeneic but unrelated H6 hepatocellular tumor cell line grew unrestricted in vaccinated mice, indicative of vaccine-mediated specific immunity to Neuro 2a tumors. Longitudinal analyses of tumor-infiltrating lymphocytes revealed a primary adaptive T cell response involving both CD4+ and CD8+ T cell subsets. Spleen cell mononuclear preparations from vaccinated mice were significantly more cytotoxic to Neuro 2a tumor cells than spleen cells from control mice as demonstrated in a four-hour in vitro cytotoxicity assay. These results strongly suggest that an irradiated whole cell tumor vaccine incorporating IL-12-expressing M002 HSV can produce a durable, specific immunization in a murine model of intracranial tumor.

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Section: Discussionmentioning

confidence: 99%

Effect of HSV-IL12 Loaded Tumor Cell-Based Vaccination in a Mouse Model of High-Grade Neuroblastoma

Bauer

Pereboeva

Gillespie

et al. 2016

Journal of Immunology Research

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“…The mice were euthanized whenever the tumor ulcerated or tumors exceeded a size of 15 mm in any of the perpendicular diameters. The tumor volume (V) was determined by using the formula, V=1/2(Length) (Width) 2 [26,27]. …”

Section: Methodsmentioning

confidence: 99%

Formulation and evaluation of oral microparticulate ovarian cancer vaccines

Tawde

Chablani

Akalkotkar

et al. 2012

Vaccine

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Ovarian cancer is the fifth most leading cause of cancer related deaths in women in the US. Customized immunotherapeutic strategies may serve as an alternative method to control the recurrence or progression of ovarian cancer and to avoid severe adverse effects of chemotherapy. In this study, a microparticulate vaccine using whole cell lysate of a murine ovarian cancer cell line, ID8 was prepared with the use of a spray dryer. These particles were designed for oral delivery using enteric polymers such as methacrylic copolymer, Eudragit® FS30D and hydroxyl propyl methyl cellulose acetate succinate. These particles were targeted for uptake via microfold cell (M-cell) in Peyer\u27s patches of small intestine using M-cell targeting ligand, Aleuria aurantia lectin. The interleukins (ILs) such as IL-2 and IL-12 were added to the vaccine formulation to further enhance the immune response. The particles obtained were of 1.58 ± 0.62 μm size with a charge of 12.48 ± 2.32 mV. The vaccine efficacy was evaluated by administering the particles via oral route to C57BL/6 female mice. At the end of vaccination, mice were challenged with live tumor cells. Vaccinated mice showed significant (around six-fold) retardation of tumor volume in comparison to non-vaccinated animals for 3 weeks after the tumor challenge (p \u3c 0.001). The serum IgG antibody levels were found to be elevated in case of vaccinated animals in comparison to non-vaccinated group (p \u3c 0.05). Analysis of IgG1 titers (indicative of Th2 response) and IgG2a titers (indicative of Th1 response) showed a mixed Th1 and Th2 immune response in case vaccine alone and Th2 response in case of vaccine with interleukins group. Moreover, CD8+ T-cell, CD4+ T-cell and B-cell populations in different lymphatic organs were elevated in case of vaccinated mice. Thus, whole cell lysate vaccine microparticles formulated by spray drying could trigger humoral as well as cellular immune response when administered orally. Such vaccine could potentially be an effective treatment for patients with residual tumor or high tumor-relapse probability

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“…One week after the last vaccination, the mice were challenged s.c. with 1x10 7 live ID8 cells as described elsewhere [36,37]. The cells were injected into the right back flank of mice.…”

Section: Tumor Challenge Studymentioning

confidence: 99%

Evaluation of microparticulate ovarian cancer vaccine via transdermal route of delivery

Tawde¹,

Chablani

Akalkotkar

et al. 2016

Journal of Controlled Release

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Ovarian cancer is the fifth most commonly occurring malignancy in women, with the highest mortality rate among all the gynecological tumors. Microparticulate vaccine can serve as an immunotherapeutic approach with a promising antigenic delivery system without a need for conventional adjuvants. In this study, a microparticulate vaccine using whole cell lysate of a murine ovarian cancer cell line, ID8 was prepared by spray drying. Further, the effect of interleukins (ILs) such as IL-2 and IL-12 was evaluated in a separate study group by administering them with vaccine particles to enhance the immune response. The vaccine microparticles were administered to C57BL/6 female mice via transdermal alone and in combination with the oral route. The transdermal vaccine was delivered using a metallic microneedle device, AdminPen™. Orally administered microparticles also included an M-cell targeting ligand, Aleuria aurantia lectin, to enhance the targeted uptake from microfold cells (M-cells) in Peyer's patches of small intestine. In case of combination of routes, mice were given 5 transdermal doses and 5 oral doses administered alternatively, beginning with transdermal dose. At the end of vaccination, mice were challenged with live tumor cells. Vaccine alone resulted in around 1.5 times tumor suppression in case of transdermal and combination of routes at the end of 15th week when compared to controls. Inclusion of interleukins resulted in 3 times tumor suppression when administered with transdermal vaccine and around 9 times tumor suppression for the combination route of delivery in comparison to controls. These results were further potentiated by serum IgG, IgG1 and IgG2a titers. Moreover, CD8+ T-cell, CD4+ T-cell and NK (natural killer) cell populations in splenocytes were elevated in case of vaccinated mice. Thus, vaccine microparticles could trigger humoral as well as cellular immune response when administered transdermally and via combination of route of delivery. However overall, vaccine administered with interleukins, via combination of route, was found to be the most efficacious to suppress the tumor growth and lead to a protective immune response.

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Direct vaccination with tumor cells killed with ICP4-deficient HSVd120 elicits effective antitumor immunity

Cited by 19 publications

References 46 publications

Effect of HSV-IL12 Loaded Tumor Cell-Based Vaccination in a Mouse Model of High-Grade Neuroblastoma

Effect of HSV-IL12 Loaded Tumor Cell-Based Vaccination in a Mouse Model of High-Grade Neuroblastoma

Formulation and evaluation of oral microparticulate ovarian cancer vaccines

Evaluation of microparticulate ovarian cancer vaccine via transdermal route of delivery

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