Nivolumab in the treatment of malignant melanoma: review of the literature

Mashima, Emi; Inoue, Akiomi; Sakuragi, Yumiko; Yamaguchi, Takashi; Sasaki, Natsuko; Hara, Yoko; Omoto, Daisuke; Ohmori, Shun; Haruyama, Sanehito; Sawada, Yu; Yoshioka, Manabu; Nishio, Daisuke; Nakamura, Motonobu

doi:10.2147/ott.s62102

Cited by 21 publications

(15 citation statements)

References 40 publications

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“…In fact, IFN-α is greatly increased in serum and in the affected tissues in patients with IgG4-related pancreatitis [ 42 ]. As a matter of fact, the transcription factor IFN regulatory factor 9 activated by IFN-α is known to bind to the promoter region of the PD-1 gene and induce PD-1 mRNA transcription [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Enhanced IgG4 production by follicular helper 2 T cells and the involvement of follicular helper 1 T cells in the pathogenesis of IgG4-related disease

et al. 2016

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BackgroundThe aim of this study was to elucidate the function of circulating follicular helper T (Tfh) cell subsets in helping B cells in patients with active, untreated IgG4-related disease (IgG4-RD) and determine their relationship with disease activity.MethodsSeventeen consecutive patients with active, untreated IgG4-RD, 20 with primary Sjögren syndrome (pSS), 5 with multicentric Castleman’s disease (MCD), and 12 healthy controls (HC) were enrolled. Tfh cell subset function was evaluated by co-culture with naïve B cells in vitro. Activated Tfh cell subsets were defined as a CCR7lowPD-1high subset among Tfh cell subsets. Disease activity was evaluated by IgG4-RD responder index (IgG4-RD RI) score.ResultsThe number of Tfh2 cells was significantly higher in IgG4-RD compared to pSS, MCD, or HC, and correlated with serum IgG4 level or the number of plasmablasts. In vitro, Tfh2 cells more efficiently induced the differentiation of naïve B cells into plasmablasts compared to Tfh1 or Tfh17 cells. Of note, while IgG production in culture supernatants of Tfh2 cells was comparable between IgG4-RD and HC, IgG4 production was significantly higher with Tfh2 cells from patients with IgG4-RD than in those from HC. Accordingly, the IgG4:IgG ratio in culture supernatants was also significantly higher with Tfh2 cells from IgG4-RD compared to HC. Moreover, the number of activated Tfh2 cells was higher in IgG4-RD compared to pSS, MCD, or HC, and strongly correlated with IgG4-RD RI score in the baseline active phase. Particularly, the number of activated Tfh2 cells was associated with the number of affected organs and serum IgG4 level. Importantly, the number of activated Tfh2 cells was decreased after glucocorticoid treatment and paralleled disease improvement. Moreover, the number of activated Tfh1 cells was also increased in IgG4-RD compared to pSS, MCD, or HC, correlating with IgG4-RD RI score, but not with serum IgG4 level.ConclusionsTfh2 cells, but not Tfh1 or Tfh17 cells, induce the differentiation of naïve B cells into plasmablasts and enhanced production of IgG4 in patients with active, untreated IgG4-RD. Furthermore, activated Tfh2 cells reflect disease activity, suggesting the involvement of this T cell subset in the pathogenesis of IgG4-RD. Interestingly, the number of activated Tfh1 cells was also increased in IgG4-RD, correlating with disease activity but not with serum IgG4 level, suggesting the involvement of Tfh1 cells but not in the process of IgG4 production in patients with IgG4-RD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1064-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Enhanced IgG4 production by follicular helper 2 T cells and the involvement of follicular helper 1 T cells in the pathogenesis of IgG4-related disease

et al. 2016

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“…Advances have been achieved in immunotherapy over the past several years, and the efficacy of immune checkpoint inhibitors, such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies, against various malignant tumors has been reported in actual clinical practice and clinical studies [ 4 ]. Regarding HBV, anti-HBs antibody-positive individuals are considered to have recovered, with reactivation being rare.…”

Section: Introductionmentioning

confidence: 99%

Immune responses of human T lymphocytes to novel hepatitis B virus-derived peptides

et al. 2018

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Background & aimsMany individuals are infected with hepatitis B virus (HBV) worldwide, and this virus is commonly controlled by treatments with interferon (IFN)-alpha and nucleoside analogues (NA). However, the complete elimination of HBV by these treatments is difficult and, thus, the development of new treatments is needed. Host immune responses are closely involved in the elimination of HBV, suggesting the usefulness of immunotherapy. In the present study, we attempted to identify novel cytotoxic T-lymphocyte (CTL) epitopes that are useful for immunotherapy against HBV.MethodsCTL epitopes were predicted using computer software. Immune responses to each peptide were evaluated by IFN-γ ELISPOT and cytotoxic assays. The relationships between the immune responses to these newly identified CTL epitopes and the clinical backgrounds of patients and administration of NA were analyzed. Peptides were administered to mice as vaccines and peptide-specific T-cell induction was measured in vivo.ResultsPositive reactions to 10 synthesized peptides were detected in 3 or more patients using the IFN-γ ELISPOT assay, and concentration-dependent cytotoxicity against 2 of these peptides was observed in the cytotoxic assay. Some peptides that correlated with serum ALT, HBsAg, and HBV core-related antigen (HBcrAg) levels were identified. Immune reactions against some peptides were enhanced by the administration of NA. Regarding their effects as a vaccine, peptide-specific T-cells were induced by four peptides in vivo.ConclusionsNovel HBV epitopes that correlated with HBsAg and HBcrAg levels were identified. These newly identified epitopes may be useful in the analysis of immune responses to HBV and development of immunotherapy against HBV.

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“…In the third phase I study, 90 patients with vaccine in ipilimumab-refractory or -naive melanoma received nivolumab at 1.0, 3.0, or 10.0 mg/kg, with or without a multipeptide vaccine 38 . Among 87 evaluable patients, the ORR for nivolumab with or without vaccine was 25% 38 , 39 . Wolchok et al also conducted a phase I trial of nivolumab combined with ipilimumab in patients with advanced melanoma, all 86 patients were enrolled in the study 40 .…”

Section: Phase Imentioning

confidence: 99%

“…In the concurrent-regimen group, 53 patients received nivolumab and ipilimumab every 3 weeks for four doses and nivolumab alone, the ORR was 40%. In the sequenced-regimen cohorts, 33 patients pretreated with ipilimumab received nivolumab every 2 weeks, the ORR was 20% 39 , 40 .…”

Section: Phase Imentioning

confidence: 99%

Nivolumab as Programmed Death-1 (PD-1) Inhibitor for Targeted Immunotherapy in Tumor

2017

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Targeted immunotherapy has become the most promising approach for tumor patients. Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, can reverse immune suppression and release T cell activation. Nivolumab, a fully human immunoglobulin G4 PD-1 immune checkpoint inhibitor antibody, blocks PD-1 and promotes antitumor immunity, and it is effective for treating non-small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC) and other cancers. The present review summarizes the efficacy and current status of clinical trials of nivolumab and that enabled nivolumab to be investigated in patients.

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Nivolumab in the treatment of malignant melanoma: review of the literature

Cited by 21 publications

References 40 publications

Enhanced IgG4 production by follicular helper 2 T cells and the involvement of follicular helper 1 T cells in the pathogenesis of IgG4-related disease

Enhanced IgG4 production by follicular helper 2 T cells and the involvement of follicular helper 1 T cells in the pathogenesis of IgG4-related disease

Immune responses of human T lymphocytes to novel hepatitis B virus-derived peptides

Nivolumab as Programmed Death-1 (PD-1) Inhibitor for Targeted Immunotherapy in Tumor

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