Inhibitory effect of the polyinosinic‐polycytidylic acid/cationic liposome on the progression of murine B16F10 melanoma

Fujimura, Taku; Nakagawa, Satoshi; Ohtani, Tomoyuki; Ito, Yumiko; Aiba, Setsuya

doi:10.1002/eji.200636053

Cited by 61 publications

(49 citation statements)

References 28 publications

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“…These findings would seem to contrast with other reports (33,34), demonstrating that local TLR ligand therapy induces expansion of systemic effectors followed by tumor infiltration and subsequent tumor growth inhibition and/or complete resolution. This observation may reflect the biology of our tumor model, in particular the observation that expanded and armed effectors appear to remain in the tumor draining lymph nodes (35).…”

Section: Requirement For Local Cd8 T Cell Responsescontrasting

confidence: 99%

Targeting the Effector Site with IFN-αβ-Inducing TLR Ligands Reactivates Tumor-Resident CD8 T Cell Responses to Eradicate Established Solid Tumors

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Broomfield

et al. 2008

The Journal of Immunology

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Effective antitumor CD8 T cell responses may be activated by directly targeting the innate immune system within tumors. We investigated this response by injecting a range of TLR agonists into established tumors using a mouse model of malignant mesothelioma stably transduced with the hemagglutinin (HA) gene as a marker Ag (AB1-HA). Persistent delivery of the dsRNA mimetic poly(I:C) into established AB1-HA tumors resulted in complete tumor resolution in 40% of mice, with the remaining mice also showing a significant delay in tumor progression. Experiments in athymic nude mice along with CD8 depletion and IFN-αβ blocking studies revealed that tumor resolution required both CD8 T cells and type I IFN induction, and was associated with local changes in MHC class I expression. Surprisingly, however, tumor resolution was not associated with systemic dissemination or tumor infiltration of effector CD8 T cells. Instead, the antitumor response was critically dependent on the reactivation of tumor-resident CD8 T cell responses. These studies suggest that, once reactivated, pre-existing local CD8 T cell responses are sufficient to resolve established tumors and that in situ type I IFN is a determining factor.

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Section: Requirement For Local Cd8 T Cell Responsescontrasting

confidence: 99%

Targeting the Effector Site with IFN-αβ-Inducing TLR Ligands Reactivates Tumor-Resident CD8 T Cell Responses to Eradicate Established Solid Tumors

Currie

Most

Broomfield

et al. 2008

The Journal of Immunology

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“…We examined the therapeutic effects of IFN-b in combination with anti-PD-1 Ab in vivo by using the established B16F10 murine melanoma model. 22,23 We treated B16F10 melanomas (5 mm in diameter) on the backs of mice by intraperitoneal injection of anti-PD-1 Ab (0.25 mg/ mouse) with or without peritumoral injection of IFN-b (10,000 U) three times a week for two weeks. For the control antibody, we used rat IgG (0.25 mg/ mouse).…”

Section: Resultsmentioning

confidence: 99%

“…In contrast to the clinical findings, in a mouse melanoma model, peritumoral administration of IFN-b does not suppress tumor growth in vivo. 22,23 This discrepancy may be explained by the immunomodulatory effect of IFN on cancer stroma. For example, IFNg augments the expression of suppressive molecules, such as PD-L1 and CD271, on the melanoma cells to suppress the activation of melanoma-specific CTLs.…”

Section: Discussionmentioning

confidence: 99%

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Immunomodulatory effect of peritumorally administered interferon-beta on melanoma through tumor-associated macrophages

et al. 2015

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These authors contributed equally to this work. Keywords: IFN-b, in-transit melanoma, PD-1, regulatory T cells, tumor-associated macrophagesAn imbalance of immunosuppressive cells and cytotoxic cells plays an important role in the tumor-bearing host. Together with regulatory T cells (Tregs), tumor-associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Since interferon beta (IFN-b) has been clinically used for the treatment of malignant melanoma, we investigated the immunomodulatory effect of IFN-b during melanoma growth to elucidate the effects of IFN-b on the tumor microenvironment by using the B16F10 melanoma model. Peritumorally administered IFN-b significantly decreased the mRNA expression and production of Th2-related chemokines, which suppressed the recruitment of Tregs in B16F10 melanoma. Since the administration of IFN-b augments the expression of PD-1 on TILs, the co-administration of anti-PD-1 Ab augmented the therapeutic effect of IFN-b for the treatment of B16F10 melanoma. Moreover, in parallel with the mouse model, in the human system, IFN-b decreased the production of Th2-related chemokines and augmented the production of Th1-related chemokines from monocyte-derived M2 macrophages. Since these immunomodulatory effects of IFN-b on macrophages were also observed in the lesional skin of human in-transit melanoma, our present data suggest one of the possible immunomodulatory effects of IFN-b and support the possibility of IFN-b in combination with anti-PD-1 Ab for the treatment of melanoma.

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“…It was also shown that the effectiveness of poly I:C as a vaccine adjuvant could be substantially improved by incorporation of liposome complexes in the vaccine (94). Finally, it was also shown that complexes of cationic liposomes and poly I:C were effective for tumor immunotherapy and induction of tumor-specific CD8 + T cell responses (95).…”

Section: Cationic Liposomes-nucleic Acid Complexes As Vaccine Adjuvantsmentioning

confidence: 99%

Liposome–nucleic acid immunotherapeutics

Dow¹

2007

Expert Opinion on Drug Delivery

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Cationic liposome-nucleic acid complexes, which were originally developed for use as non-viral gene delivery vectors, may now have an equally important application as immunotherapeutic drugs. Recent studies have highlighted the ability of cationic liposomes to markedly potentiate activation of the innate immune system by certain Toll-like receptor (TLR) agonists. The immune enhancing properties of cationic liposomes are most obvious when they are combined with nucleic acid agonists for endosomally-located TLRs, including TLR3, TLR7/8, and TLR9. How this immune potentiation by cationic liposomes is mediated is not completely understood, but is thought to reflect the combined effects of more efficient endosomal targeting, protection from extracellular degradation, and signaling through newly identified cytoplasmic receptors for nucleic acids. The potent innate immune stimulatory properties of liposome-nucleic acid complexes make them particularly effective as immunotherapeutics or vaccine adjuvants. As stand-alone immunotherapeutics, liposome-nucleic acid complexes have demonstrated impressive anti-cancer activity in a number of different animal tumor models. Moreover, liposome-nucleic acid complexes also show promise for immunotherapy of acute viral and bacterial infections and chronic fungal infections. When used as vaccine adjuvants, liposome-nucleic acid complexes target antigens for efficient uptake by dendritic cells and are particularly effective in eliciting T cell responses. Thus, cationic liposomes combined with nucleic acids form the basis for a potent and versatile immunotherapeutic platform.

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Inhibitory effect of the polyinosinic‐polycytidylic acid/cationic liposome on the progression of murine B16F10 melanoma

Cited by 61 publications

References 28 publications

Targeting the Effector Site with IFN-αβ-Inducing TLR Ligands Reactivates Tumor-Resident CD8 T Cell Responses to Eradicate Established Solid Tumors

Targeting the Effector Site with IFN-αβ-Inducing TLR Ligands Reactivates Tumor-Resident CD8 T Cell Responses to Eradicate Established Solid Tumors

Immunomodulatory effect of peritumorally administered interferon-beta on melanoma through tumor-associated macrophages

Liposome–nucleic acid immunotherapeutics

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