Melan-A/MART-1 (26-35) peptide (EAAGIGILTV) – Melanoma-Associated Antigen
Native Melan-A (26-35) decapeptide derives from the melanocyte lineage-specific protein Melan-A/MART-1, which is expressed in almost 75-100% of primary and metastatic melanomas1.
The region 26-35 of Melan-A protein acts as an antigenic peptide that is recognized by CD8+ tumor-reactive cytolytic T lymphocytes (CTLs) for designing antigen-specific cancer vaccines1. It has been shown that CD8+ Melan-A-specific CTLs isolated from melanoma patients efficiently lyse the Melan-A-expressing HLA-A*0201+ melanoma cell line. However, CTLs preferentially recognize the Melan-A (26-35) peptide as compared with the Melan-A (27-35) peptide1. Moreover, the Melan-A (26-35) A27L analog (ELAGIGILTV) has a higher binding affinity to HLA-A*0201 than the native Melan-A (26-35) peptide (EAAGIGILTV), and consequently displays more potent antigenicity and immunogenicity1.
It has been reported that the concentration of Melan-A (26-35) A27L analog required to obtain 50% of maximal antigenic activity (EC50) is 0.01nM, whereas that of the native Melan-A (26-35) peptide is 0.25nM1. Therefore, the relative activity of Melan-A (26-35) A27L analog is 25 fold higher than that of the native Melan-A (26-35) peptide.
Furthermore, functional competition assay has shown that the concentration of Melan-A (26-35) A27L analog required to achieve 50% inhibition (IC50) of tumor lysis is 2nM, which is 10 fold lower than that of the native Melan-A (26-35) peptide1. Regarding peptide stability in human serum, the half-lifes (t1/2) of the native Melan-A (26-35) peptide and the A27L analog are quite similar (45 and 40min, respectively) as measured by HPLC-ESI-MS, but much higher than that of the Melan-A (27-35) nonapeptide (5min)1.
SB-PEPTIDE offers the scrambled version of Melan-A/MART-1 (26-35) peptide (see section « Melan-A/MART-1 (26-35) scrambled »).
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1- Blanchet, J.-S. et al. J. Immunol. 167, 5852–5861 (2001)
A new generation of Melan-A/MART-1 peptides that fulfill both increased immunogenicity and high resistance to biodegradation: implication for molecular anti-melanoma immunotherapy
Intense efforts of research are made for developing antitumor vaccines that stimulate T cell-mediated immunity. Tumor cells specifically express at their surfaces antigenic peptides presented by MHC class I and recognized by CTL. Tumor antigenic peptides hold promise for the development of novel cancer immunotherapies. However, peptide-based vaccines face two major limitations: the weak immunogenicity of tumor Ags and their low metabolic stability in biological fluids. These two hurdles, for which separate solutions exist, must, however, be solved simultaneously for developing improved vaccines. Unfortunately, attempts made to combine increased immunogenicity and stability of tumor Ags have failed until now. Here we report the successful design of synthetic derivatives of the human tumor Ag Melan-A/MART-1 that combine for the first time both higher immunogenicity and high peptidase resistance. A series of 36 nonnatural peptide derivatives was rationally designed on the basis of knowledge of the mechanism of degradation of Melan-A peptides in human serum and synthesized. Eight of them were efficiently protected against proteolysis and retained the antigenic properties of the parental peptide. Three of the eight analogs were twice as potent as the parental peptide in stimulating in vitro Melan-specific CTL responses in PBMC from normal donors. We isolated these CTL by tetramer-guided cell sorting and expanded them in vitro. The resulting CTL efficiently lysed tumor cells expressing Melan-A Ag. These Melan-A/MART-1 Ag derivatives should be considered as a new generation of potential immunogens in the development of molecular anti-melanoma vaccines.