Interferon-γ therapy: Evaluation of routes of administration and delivery systems

Younes, Husam M.; Amsden, Brian G.

doi:10.1002/jps.10007.abs

Cited by 12 publications

(15 citation statements)

References 33 publications

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“…Both IFNg and GM-CSF are important for the recruitment and activation of immune cells to the immunization site. Being aware of their respectively short half-life in vivo, [28][29][30] we were interested to examine their potential role in the initiation of a systemic antitumor immune response after immunization. Therefore, the pharmacokinetics for both cytokines after i.p.…”

Section: Resultsmentioning

confidence: 99%

Cure of established GL261 mouse gliomas after combined immunotherapy with GM‐CSF and IFNγ is mediated by both CD8⁺ and CD4⁺ T‐cells

Smith

Fritzell

Badn

et al. 2008

Intl Journal of Cancer

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We were the first to demonstrate that combined immunotherapy with GM-CSF producing GL261 cells and recombinant IFNc of preestablished GL261 gliomas could cure 90% of immunized mice. To extend these findings and to uncover the underlying mechanisms, the ensuing experiments were undertaken. We hypothesized that immunizations combining both GM-CSF and IFNc systemically would increase the number of immature myeloid cells, which then would mature and differentiate into dendritic cells (DCs) and macrophages, thereby augmenting tumor antigen presentation and T-cell activation. Indeed, the combined therapy induced a systemic increase of both immature and mature myeloid cells but also an increase in T regulatory cells (T-regs). Cytotoxic anti-tumor responses, mirrored by an increase in Granzyme B-positive cells as well as IFNc-producing T-cells, were augmented after immunizations with GM-CSF and IFNc. We also show that the combined therapy induced a long-term memory with rejection of intracerebral (i.c.) rechallenges. Depletion of Tcells showed that both CD4 1 and CD8 1 T-cells were essential for the combined GM-CSF and IFNc effect. Finally, when immunizations were delayed until day 5 after tumor inoculation, only mice receiving immunotherapy with both GM-CSF and IFNc survived. We conclude that the addition of recombinant IFNc to immunizations with GM-CSF producing tumor cells increased the number of activated tumoricidal T-cells, which could eradicate established intracerebral tumors. These results clearly demonstrate that the combination of cytokines in immunotherapy of brain tumors have synergistic effects that have implications for clinical immunotherapy of human malignant brain tumors.

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Section: Resultsmentioning

confidence: 99%

Cure of established GL261 mouse gliomas after combined immunotherapy with GM‐CSF and IFNγ is mediated by both CD8⁺ and CD4⁺ T‐cells

Smith

Fritzell

Badn

et al. 2008

Intl Journal of Cancer

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“…Interferon gamma (IFN‐γ) is the type II class of cytokine majorly secreted by the natural killer CD4 and CD8 cytotoxic T1 lymphocytes. It possesses anti‐proliferative, pro‐inflammatory, and immunomodulatory effects, which is why the U.S. FDA has approved this drug for the treatment of chronic granulomatous disease (CGD) and severe malignant osteopetrosis in children and adults . Mature human interferon‐gamma consists of 143 amino acids with a molecular weight of 17–24 kDa, depending upon the glycosylation pattern.…”

Section: Introductionmentioning

confidence: 99%

Artificial neural network‐genetic algorithm (ANN‐GA) based medium optimization for the production of human interferon gamma (hIFN‐γ) in Kluyveromyces lactis cell factory

et al. 2019

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In the current investigation, we have adapted response surface methodology (RSM) and artificial neural network-genetic algorithm (ANN-GA) based optimization to develop a defined medium for maximizing human interferon gamma production from recombinant Kluyveromyces lactis (K. lactis).In the initial screening studies, sorbitol and glycine emerged as a carbon and nitrogen source respectively having higher influence on hIFN-g production. Substrate inhibition studies were performed by varying the initial substrate concentration, and we found maximum hIFN-g concentration at 50 g L À1 of sorbitol. Inhibition kinetics studies were carried out using 3 and 4-parametric models. Among the estimated models, the Moser model was observed as the best fitted model followed by the Luong model with R 2 values of 0.882 and 0.75, respectively. The model acceptability test was carried out using the extra sum of squares F-test and Akaike information criterion (AIC). The Plackett-Burman multifactorial design identified sorbitol, glycine, Na 2 HPO 4 , and MgSO 4 .7H 2 O as the parameters significantly influencing the hIFN-g production. Further, the Box-Behnken design (BBD) followed by the artificial neural network coupled with genetic algorithm (ANN-GA) was employed for the precise optimization of medium components. With ANN-GA a maximum hIFN-g yield of 2.1 AE0.3 mg L À1 in shake flask level and 3.5 AE0.1 mg L À1 in reactor level was achieved. The findings of this study serve as a model for a process development strategy (bench scale to reactor scale) to achieve a high productivity of the desired protein from a microbial cell factory.

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“…Their high compliance and creep resistance are highly desired properties when culturing cardiovascular cells in a dynamic environment, such as in a pulsatile flow cell culturing bioreactor. These polymers have been applied in the controlled delivery of drugs,7 genes,8 cytokines,9 and growth factors10 as well.…”

Section: Introductionmentioning

confidence: 99%

In vivo behavior of trimethylene carbonate and ε‐caprolactone‐based (co)polymer networks: Degradation and tissue response

Bat

Plantinga

Harmsen

et al. 2010

J Biomedical Materials Res

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The in vivo erosion behavior of crosslinked (co)polymers based on trimethylene carbonate (TMC) and ε-caprolactone (CL) was investigated. High molecular weight poly(trimethylene carbonate) (PTMC) homopolymer- and copolymer films were crosslinked by gamma irradiation. To adjust the in vivo erosion rate of the (co)polymer films, both the irradiation dose (25, 50, or 100 kGy) for PTMC and composition (100-70 mol % TMC) at a constant irradiation dose of 25 kGy were varied. After subcutaneous implantation of irradiated films in rats, their in vivo behavior was evaluated qualitatively and quantitatively. When the irradiation dose for PTMC was increased from 25 to 100 kGy, the erosion rate of nonextracted PTMC films (determined at day 5) decreased from 39.7 ± 16.0 μm day(-1) to 15.1 ± 2.5 μm day(-1), and the number of lymphocytes in the tissue surrounding the films decreased from 235 ± 114 cells mm(-2) to 64 ± 33 cells mm(-2). The number of macrophages and giant cells at the tissue-polymer interface also decreased with increasing irradiation dose. All (co)polymer films eroded completely within 28 days of implantation. Variation of the TMC content of gamma irradiated (co)polymer films did not affect the tissue response to the gamma irradiated (co)polymer films and their in vivo erosion behavior much.

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Interferon-γ therapy: Evaluation of routes of administration and delivery systems

Cited by 12 publications

References 33 publications

Cure of established GL261 mouse gliomas after combined immunotherapy with GM‐CSF and IFNγ is mediated by both CD8⁺ and CD4⁺ T‐cells

Cure of established GL261 mouse gliomas after combined immunotherapy with GM‐CSF and IFNγ is mediated by both CD8⁺ and CD4⁺ T‐cells

Artificial neural network‐genetic algorithm (ANN‐GA) based medium optimization for the production of human interferon gamma (hIFN‐γ) in Kluyveromyces lactis cell factory

In vivo behavior of trimethylene carbonate and ε‐caprolactone‐based (co)polymer networks: Degradation and tissue response

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Interferon-γ therapy: Evaluation of routes of administration and delivery systems

Cited by 12 publications

References 33 publications

Cure of established GL261 mouse gliomas after combined immunotherapy with GM‐CSF and IFNγ is mediated by both CD8+ and CD4+ T‐cells

Cure of established GL261 mouse gliomas after combined immunotherapy with GM‐CSF and IFNγ is mediated by both CD8+ and CD4+ T‐cells

Artificial neural network‐genetic algorithm (ANN‐GA) based medium optimization for the production of human interferon gamma (hIFN‐γ) in Kluyveromyces lactis cell factory

In vivo behavior of trimethylene carbonate and ε‐caprolactone‐based (co)polymer networks: Degradation and tissue response

Contact Info

Product

Resources

About

Cure of established GL261 mouse gliomas after combined immunotherapy with GM‐CSF and IFNγ is mediated by both CD8⁺ and CD4⁺ T‐cells

Cure of established GL261 mouse gliomas after combined immunotherapy with GM‐CSF and IFNγ is mediated by both CD8⁺ and CD4⁺ T‐cells