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).
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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
B.A. Ksander, 1991: Studies of tumour infiltrating lymphocytes from a human choroidal melanoma. Invest Ophthalmol Vis Sci 32, 3798–3208
K.A. Mulcahy, 1996: Infrequent expression of the MAGE gene family in uveal melanomas. Int J Cancer 66, 738–742
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
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
T. Woefel, 1994: Two tyrosine nonapeptides recognised on HLA-A2 melanomas by autologous cytolytic T-lymphocytes. Eur J Immunol 24, 759–764
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
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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
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