Expression of cancer-testis antigens (MAGE-A1, MAGE-A3/6, MAGE-A4, MAGE-C1 and NY-ESO-1) in primary human uveal and conjunctival melanoma

Errington, Jodie A; Conway, R.; Walsh-Conway, N; Browning, Judy; Freyer, Claudia; Cebon, Jonathan; Madigan, Michele C.

doi:10.1136/bjophthalmol-2011-300432

Cited by 24 publications

(5 citation statements)

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“… 1,5,18 Furthermore, the overall mutational load is significantly lower 5 compared to CM 3 and expression of cancer-testis antigens is significantly rarer. 19 Consequently, the number and quality of (neo-)antigens presented to the immune system is likely to be different. Additionally, UM may rely on different immune escape mechanisms most clearly evidenced by the observation that higher numbers of infiltrating T-cells in the primary are linked to a worse outcome.…”

Section: Introductionmentioning

confidence: 99%

Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma

et al. 2016

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Background: Untreated metastatic uveal melanoma (UM) carries a grave prognosis. Unlike cutaneous melanoma (CM), there are no established treatments known to significantly improve outcomes for a meaningful proportion of patients. Inhibition of the PD1–PDL1 axis has shown promise in the management of CM and we here report a two center experience of UM patients receiving pembrolizumab. Methods: To assess the efficacy and safety of pembrolizumab, we retrospectively analyzed outcome data of 25 consecutive UM patients participating in the MK3475 expanded access program (EAP) who received pembrolizumab at 2 mg/kg 3 weekly. Tumor assessment was evaluated using RECIST 1.1 and immune-related Response Criteria (irRC) by CT scanning. Toxicity was recorded utilizing Common Terminology Criteria for Adverse Events (“CTCAE”) v4.03. Results: Twenty-five patients were identified receiving a median of six cycles of treatment. Two patients achieved a partial response and six patients stable disease. After a median follow-up of 225 d median progression free survival (PFS) was 91 d and overall survival (OS) was not reached. There was a significant trend for improved outcomes in patients with extrahepatic disease progression as opposed to liver only progression at the outset. Five patients experienced grade 3 or 4 adverse events (AEs); there were no treatment related deaths. Conclusions: Pembrolizumab 2mg/kg q3w is a safe option in UM patients. Disease control rates, particularly in the subgroup of patients without progressive liver disease at the outset are promising; these results merit further investigation in clinical trials possibly incorporating liver targeted treatment modalities.

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Section: Introductionmentioning

confidence: 99%

Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma

et al. 2016

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“…Recurrences are associated with an increased risk of metastatic disease often unresponsive to conventional treatment. The mortality rate following the diagnosis of CM is 15% after 5 years and 30% after 10 years, with metastatic disease as the main cause of death [6]. Therefore, more effective treatments are needed in order to prevent local recurrence or the development of metastases.…”

Section: Introductionmentioning

confidence: 99%

Expression of Multidrug Resistance Transporter ABCB5 in a Murine Model of Human Conjunctival Melanoma

et al. 2015

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Conjunctival melanoma (CM) is a rare ocular malignancy with a high tendency to reoccur locally and with a high risk of metastatic disease. Metastases are often unresponsive to conventional treatment. Recently, an animal model was set up using human CM cells. Orthotopic xenografts from human CM were created by subconjunctival injection of three different CM cell lines into NOD.Cg-Prkdc^scid IL2rg^tm1Wjl/SzJ (NSG) mice. Subconjunctival injection of cultured CM cells led to excellent subconjunctival growth, but no metastases were found. When single-cell suspensions were obtained from the subconjunctival xenografts and passaged in vivo, all mice developed metastases. As recent findings indicate that cancer stem cells are linked to tumor recurrences, we used this new murine model to determine the expression of the stem cell marker ABCB5 during tumor progression. Expression of the ABCB5 protein was determined in three cell lines and during different stages of tumor development as observed in our model. All three cell lines contained a subpopulation of cells positive for ABCB5. During tumor development, expression of ABCB5 increased during phases of tumor expansion. Furthermore, expression of ABCB5 was increased in metastases. Using this model for CM, we were able to initiate metastatic spread and determine the expression of the stem cell marker ABCB5 during different stages of tumor development, identifying ABCB5 as a potential novel therapeutic target. This study illustrates the potential of our newly established murine model.

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“…MAGEA1 and MAGEB2 - are members of CT antigens; in particular, MAGEA1 was found expressed in 10% of cancer cells in conjunctival melanomas [31], and could be another candidate working in combination with immunotherapy;…”

Section: Resultsmentioning

confidence: 99%

Pathway landscapes and epigenetic regulation in breast cancer and melanoma cell lines

Baroudi

Sala

Cinti

et al. 2014

Theor Biol Med Model

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BackgroundEpigenetic variation is a main regulation mechanism of gene expression in various cancer histotypes, and due to its reversibility, the potential impact in therapy can be very relevant.MethodsBased on a selected pair, breast cancer (BC) and melanoma, we conducted inference analysis in parallel on a few cell lines (MCF-7 for BC and A375 for melanoma). Starting from differential expression after treatment with a demethylating agent, the 5-Aza-2'-deoxycytidine (DAC), we provided pathway enrichment analysis and gene regulatory maps with cross-linked microRNAs and transcription factors.ResultsSeveral oncogenic signaling pathways altered upon DAC treatment were detected with significant enrichment. We represented the association between these cancers by depicting the landscape of common and specific variation affecting them.

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Expression of cancer-testis antigens (MAGE-A1, MAGE-A3/6, MAGE-A4, MAGE-C1 and NY-ESO-1) in primary human uveal and conjunctival melanoma

Cited by 24 publications

References 33 publications

Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma

Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma

Expression of Multidrug Resistance Transporter ABCB5 in a Murine Model of Human Conjunctival Melanoma

Pathway landscapes and epigenetic regulation in breast cancer and melanoma cell lines

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