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Recognition of Melanoma-Associated Peptides by Peripheral Blood Mononuclear Cells of Ocular Melanoma Patients

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Gene Therapy of Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 451))

Abstract

Melanoma of the eye is the most common intraocular malignancy in adults with approximately 50% of patients subsequently developing metastases, usually of the liver. In the United Kingdom there are 300–400 new cases of ocular/uveal melanoma each year. Tumour-associated antigens have been described for ocular melanoma and there is evidence to suggest that choroidal melanoma cells can elicit an immune response to tumour antigens [1]. It has already been shown that although uveal melanoma cells do not express the MAGE genes, they do express high levels of the melanocyte lineage specific genes, tyrosinase, gp100 and melan-A/MART-1 [2] (Table 1). Three nonamer melanoma-associated peptides, restricted by HLA-A0201, were selected from the genes tyrosinase, gp100 and melan-A/MART-1, for the study, and coded, T9368, G9280 and M927 respectively [4-6] (Table 2). These peptides were considered most suitable for the study since, HLA-A0201 is the most frequently expressed Class I allele (49% of Caucasians), and they have been shown to have both the ability to bind to HLA-A0201, and are capable of eliciting a CTL response, restricted by this haplotype, in cutaneous melanoma (Table 2).

Table 1. Expression of melanoma antigen genes in primary uveal melanomas [2]

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Abbreviations

APC:

antigen presenting cells

CB:

cilary body derived tumour

CTL:

cytotoxic T-lymphocytes

DMSO:

dimethyl sulfoxide

F(ab’)2 :

divalent antigen binding fragment after pepsin digestion

FITC:

fluorescein isothiocyanate

FR:

fluorescence ratio

gp100:

melanocyte lineage specific gene encoding glycoprotein

HLA:

human leukocyte antigen

HPLC:

high performance liquid chromatography

IgG:

immunoglobulin G

IL-2:

interleukin-2

K562:

myeloid leukaemia cell line

MAGE:

melanoma antigen E

MART-1:

melanoma antigen recognised by T-lymphocytes

melan-A:

melanocyte lineage specific gene

Mab:

monoclonal antibody

MHC:

major histocompatibility complex

PBMC:

peripheral blood mononuclear cells

PBS:

phosphate buffered saline

RPMI-1640:

culture medium

RTPCR:

reverse transcriptase polymerase chain reaction

References

  1. B.A. Ksander, 1991: Studies of tumour infiltrating lymphocytes from a human choroidal melanoma. Invest Ophthalmol Vis Sci 32, 3798–3208

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  2. K.A. Mulcahy, 1996: Infrequent expression of the MAGE gene family in uveal melanomas. Int J Cancer 66, 738–742

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  3. C.A. Mclntyre, 1996: Identification of peptide epitopes of MAGE-1, MAGE-2, and MAGE-3 that demonstrate HLA-A3-specific binding. Cancer Immunol and Immunother 42, 246–250

    Article  Google Scholar 

  4. A.B.H. Baker, 1994: Melanocyte lineage specific antigen gp100 is recognised by the majority of HLA-A2 restricted tumour infiltrating lymphocytes. J Exp Med 180, 347

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  5. T. Woefel, 1994: Two tyrosine nonapeptides recognised on HLA-A2 melanomas by autologous cytolytic T-lymphocytes. Eur J Immunol 24, 759–764

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  6. P. Coulie, 1994: A new gene coding for a differentiation antigen recognised by autologous cytolytic T-lym-phocytes on the HLA-A2 melanomas. J Exp Med 180, 35–42

    Article  PubMed  CAS  Google Scholar 

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© 1998 Springer Science+Business Media New York

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Saba, J., McIntyre, C.A., Rees, R.C., Murray, A.K. (1998). Recognition of Melanoma-Associated Peptides by Peripheral Blood Mononuclear Cells of Ocular Melanoma Patients. In: Walden, P., Trefzer, U., Sterry, W., Farzaneh, F., Zambon, P. (eds) Gene Therapy of Cancer. Advances in Experimental Medicine and Biology, vol 451. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5357-1_38

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  • DOI: https://doi.org/10.1007/978-1-4615-5357-1_38

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7444-2

  • Online ISBN: 978-1-4615-5357-1

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