Identification of immunogenic MAGED4B peptides for vaccine development in oral cancer immunotherapy

Lim, Ka Keat; Chun, Nicole A. L.; Gan, Chai Phei; Teo, Soo‐Hwang; Rahman, Zainal Ariff Abdul; Abraham, Mannil Thomas; Zain, Rosnah Binti; Cheong, Sok Ching

doi:10.4161/hv.29226

Cited by 13 publications

(16 citation statements)

References 40 publications

(40 reference statements)

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“…MAGED4B peptides induce antitumor immune responses, advocating that they could be further developed as vaccine candidates for the treatment of SCC. 26 …”

Section: Discussionmentioning

confidence: 99%

Impact of combined treatment with nimesulide and cisplatin on oral carcinoma cells

Barać¹,

Mitulović

Hallström

et al. 2017

OTT

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BackgroundDespite significant advances in diagnosis and therapy, the rate of survival of patients with oral cancers still remains poor as an appropriate treatment has not been found yet, due to side effects of chemo/radiotherapy.AimThis study aimed to identify molecular mechanisms of cell death of oral cancer cells caused by treatment with a nonselective Cox-2 inhibitor in combination with a low-dose chemotherapeutic drug.MethodsSquamous cell carcinoma (SCC) cells SCC9 and SCC25 were subjected to mono- and combination therapy with nimesulide and cisplatin. Fluorescence-activated cell sorting (FACS), immunohistochemistry, high-pressure liquid chromatography (HPLC), microarray gene chips, and isobaric tags for a relative and absolute quantitation (iTRAQ) system were used.ResultsIncreased numbers of apoptotic and necrotic SCC9/SCC25 cells were detected after combined exposure. ATP levels and the energy charge of SCC9 cells were significantly decreased after both individual and combined treatment. We detected and quantified a responsible gene, keratin 6a, and 540 relevant proteins. In SCC25 cells, ATP levels significantly decreased only after combination therapy. After combined treatment of SCC9 cells, significant upregulation of Histon-H2A/H2B/H4 was found, with a local discovery false rate of 0.003 for Histon-H2A and 0.0027 for Histon-H2B, respectively.ConclusionCompared to the single-drug treatment, combined treatment of the oral cancer cells with nimesulide and cisplatin increases and induces necrosis and apoptosis through different pathways. A significant effect of the cytoplasmic increase was also observed in histones of cell lines SCC9 and SCC25 that were previously treated with combined nimesulide and cisplatin therapy.

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“…MAGED4B peptides induce antitumor immune responses, advocating that they could be further developed as vaccine candidates for the treatment of SCC. 26 …”

Section: Discussionmentioning

confidence: 99%

Impact of combined treatment with nimesulide and cisplatin on oral carcinoma cells

Barać¹,

Mitulović

Hallström

et al. 2017

OTT

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“…ELISPOT is an indirect measurement of cytotoxic potential, but it has been shown to have better sensitivity, particularly in a low effector: target ratio setting and useful when cancer patients have low lymphocyte count and limited PBMCs. This method has also reported to have an excellent correlation (R 2 = 0.95) with cytotoxicity measured using the 51 Cr-release assay [ 50 ] and was used as an indicator of functional activity of T-cells [ 65 – 66 ]. Although we observed lower number of inherent FJX1-specific T-cells in patients prior to peptide stimulation compared to healthy donors in the ex vivo ELISPOT assay, an increased number of FJX1-specific-cytokine secreting CTLs were detected in all patients (n = 4) after stimulation with peptides.…”

Section: Discussionmentioning

confidence: 99%

Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma

et al. 2015

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Nasopharyngeal carcinoma (NPC) is highly prevalent in South East Asia and China. The poor outcome is due to late presentation, recurrence, distant metastasis and limited therapeutic options. For improved treatment outcome, immunotherapeutic approaches focusing on dendritic and autologous cytotoxic T-cell based therapies have been developed, but cost and infrastructure remain barriers for implementing these in low-resource settings. As our prior observations had found that four-jointed box 1 (FJX1), a tumor antigen, is overexpressed in NPCs, we investigated if short 9–20 amino acid sequence specific peptides matching to FJX1 requiring only intramuscular immunization to train host immune systems would be a better treatment option for this disease. Thus, we designed 8 FJX1-specific peptides and implemented an assay system to first, assess the binding of these peptides to HLA-A2 molecules on T2 cells. After, ELISPOT assays were used to determine the peptides immunogenicity and ability to induce potential cytotoxicity activity towards cancer cells. Also, T-cell proliferation assay was used to evaluate the potential of MHC class II peptides to stimulate the expansion of isolated T-cells. Our results demonstrate that these peptides are immunogenic and peptide stimulated T-cells were able to induce peptide-specific cytolytic activity specifically against FJX1-expressing cancer cells. In addition, we demonstrated that the MHC class II peptides were capable of inducing T-cell proliferation. Our results suggest that these peptides are capable of inducing specific cytotoxic cytokines secretion against FJX1-expressing cancer cells and serve as a potential vaccine-based therapy for NPC patients.

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“…Interestingly, the overexpression of this molecule promotes cell migration, cell growth, and conferred resistance to apoptosis [110]. Synthetic peptides of MAGED4B have binding affinity against the MHC-Class I molecules and enhacned IFN-γ and Granzyme-B production in blood cells from OSCC patients, demonstrating that they are immunogenic; furthermore the peptide-pulsed dendritic cells enhance T-cell cytotoxicity against MAGED4B-overexpressing OSCC cell lines, demonstrating that they could be promising candidates of vaccination for OSCC treatment [10]. In OSCCs, the expression of MAGE A subfamilies A1-A12 is significantly associated with their malignancy and could be potential targets for cancer immunotherapy [111].…”

Section: Therapeutic Approachesmentioning

confidence: 99%

“…Clinical trials with blocking antibodies against IL-1α, or vaccination against tumor-specific melanoma-associated antigens have been reported [9,10]. The most promising approach activating antitumor immunity is the blockade of the PD-1/PD-L1 axis.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory aspects in the progression and treatment of oral malignancy

Kondoh

Mizuno‐Kamiya

Umemura

et al. 2019

Japanese Dental Science Review

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Inflammation substantially affects the risk of oral malignancy. Pro-inflammatory cytokine, interferon (IFN)-γ, confers anti-tumor activity using several different mechanisms. Conversely, higher expression of interleukin (IL)-17 is associated with worse prognosis. Monocyte chemotactic protein (MCP)-1 correlates positively with poor long-term survival of head and neck squamous cell carcinoma (HNSCC) patients. IL-1α affects cancer associated fibroblasts and macrophages, and promote several malignant phenotypes including immune suppression. Some anti-inflammatory cytokines, including IL-10 and transforming growth factor (TGF)-β, relate to pro-tumoral activities.Among immune checkpoint modulators, programmed death (PD-)1 and PD-ligand (L)1 facilitate oral squamous cell carcinoma (OSCC) cell evasion from immune surveillance, and the expression status of these has a prognostic value.OSCCs contain tumor associated macrophages (TAMs) as major stromal cells of their tumor microenvironment. Among the two distinctive states, M2 macrophages support tumor invasion, metastasis and immune suppression. Crosstalk between TAMs and OSCC or cancer-associated fibroblasts (CAF) plays an important role in the progression of OSCC.Clinical trials with blocking antibodies against IL-1α or melanoma-associated antigens have been reported as therapeutic approaches against OSCCs. The most promising approach activating antitumor immunity is the blockade of PD-1/PD-L1 axis. Manipulating the polarization of pro-tumorigenic macrophages has been reported as a novel therapeutic approach.

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Identification of immunogenic MAGED4B peptides for vaccine development in oral cancer immunotherapy

Cited by 13 publications

References 40 publications

Impact of combined treatment with nimesulide and cisplatin on oral carcinoma cells

Impact of combined treatment with nimesulide and cisplatin on oral carcinoma cells

Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma

Immunomodulatory aspects in the progression and treatment of oral malignancy

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