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MELOE-1 is a new antigen overexpressed in melanomas and involved in adoptive T cell transfer efficiency.

Godet Y, Moreau-Aubry A, Guilloux Y, Vignard V, Khammari A, Dreno B, Jotereau F, Labarriere N - J. Exp. Med. (2008)

Bottom Line: Remarkably, the structure of meloe was unusual, with multiple short open reading frames (ORFs).The peptide recognized by the CTL clone was encoded by one of these ORFs, called MELOE-1.Using a specific HLA-A2/peptide tetramer, we showed a correlation between the infusion of TILs containing MELOE-1-specific T cells and relapse prevention in HLA-A2 patients.

View Article: PubMed Central - PubMed

Affiliation: Institut National de Santé et de Recherche Médicale, Unité Mixte de Recherche 892, 44093 Nantes, France.

ABSTRACT
A cytotoxic T lymphocyte (CTL) clone was derived from a tumor-infiltrating lymphocyte (TIL) population infused to a melanoma patient who remained relapse free for 10 yr after this adoptive transfer. This clone recognized all melanoma cell lines tested and, to a lower extent, melanocytes, in the context of human histocompatibility leukocyte antigen A2 (HLA-A2), but it did not recognize other tumor cell types. The gene coding for the antigen recognized by this clone was identified by the screening of a melanoma complementary DNA expression library. This antigen is overexpressed in melanomas, compared with other cancer cell lines and healthy tissues, and was thus called melanoma-overexpressed antigen (meloe). Remarkably, the structure of meloe was unusual, with multiple short open reading frames (ORFs). The peptide recognized by the CTL clone was encoded by one of these ORFs, called MELOE-1. Using a specific HLA-A2/peptide tetramer, we showed a correlation between the infusion of TILs containing MELOE-1-specific T cells and relapse prevention in HLA-A2 patients. Indeed, 5 out of 9 patients who did not relapse were infused with TILs that contained MELOE-1-specific T cells, whereas 0 out of the 21 patients who relapsed was infused with such TIL-containing lymphocytes. Overall, our results suggest that this new antigen is involved in immunosurveillance and, thus, represents an attractive target for immunotherapy protocols of melanoma.

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Characterization of meloe-derived peptide recognized by the M170.48 T cell clone. (A) Structure of meloe cDNA. Boxes illustrate ORFs >120 bp present along the meloe sequence, and black boxes correspond to ORFs tested for recognition by the CTL clone. (B) M170.48 TNF responses to COS-7 cells (E/T ratio = 1:3) transfected with the indicated plasmids. The T cell clone was added 2 d after the transfection, and the CTL clone reactivity was assessed by a TNF release assay. (C) Nucleotide and amino acid sequences of the ORF 1,230–1,370 of meloe isolated from the M134 cDNA library. The two candidate peptides are bolded. (D) Cytotoxicity of the M170.48 CTL clone against peptide-pulsed T2 cells. Target cells were 51Cr-labeled for 60 min and incubated for 30 min with a range of the indicated peptides. The M170.48 T cell clone was added (E/T ratio = 10:1), and chromium release was then measured after a 4-h incubation period.
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fig3: Characterization of meloe-derived peptide recognized by the M170.48 T cell clone. (A) Structure of meloe cDNA. Boxes illustrate ORFs >120 bp present along the meloe sequence, and black boxes correspond to ORFs tested for recognition by the CTL clone. (B) M170.48 TNF responses to COS-7 cells (E/T ratio = 1:3) transfected with the indicated plasmids. The T cell clone was added 2 d after the transfection, and the CTL clone reactivity was assessed by a TNF release assay. (C) Nucleotide and amino acid sequences of the ORF 1,230–1,370 of meloe isolated from the M134 cDNA library. The two candidate peptides are bolded. (D) Cytotoxicity of the M170.48 CTL clone against peptide-pulsed T2 cells. Target cells were 51Cr-labeled for 60 min and incubated for 30 min with a range of the indicated peptides. The M170.48 T cell clone was added (E/T ratio = 10:1), and chromium release was then measured after a 4-h incubation period.

Mentions: The meloe cDNA does not contain a long open reading frame (ORF) but multiple short ORFs. ORFs longer than 90 bp are illustrated in Fig. 3 A. The putative ORF described by the NIH Mammalian Gene Collection consortium was located between 486 and 689 bp (21). We tested this ORF and three additional ORFs (Fig. 3 A, black boxes) for recognition by M170.48, after transfection into COS-7 cells, with the HLA-A*0201 cDNA (Fig. 3 B). The ORFs tested (Table II) were chosen on the basis of preliminary results obtained on PCR fragments of meloe (unpublished data).


MELOE-1 is a new antigen overexpressed in melanomas and involved in adoptive T cell transfer efficiency.

Godet Y, Moreau-Aubry A, Guilloux Y, Vignard V, Khammari A, Dreno B, Jotereau F, Labarriere N - J. Exp. Med. (2008)

Characterization of meloe-derived peptide recognized by the M170.48 T cell clone. (A) Structure of meloe cDNA. Boxes illustrate ORFs >120 bp present along the meloe sequence, and black boxes correspond to ORFs tested for recognition by the CTL clone. (B) M170.48 TNF responses to COS-7 cells (E/T ratio = 1:3) transfected with the indicated plasmids. The T cell clone was added 2 d after the transfection, and the CTL clone reactivity was assessed by a TNF release assay. (C) Nucleotide and amino acid sequences of the ORF 1,230–1,370 of meloe isolated from the M134 cDNA library. The two candidate peptides are bolded. (D) Cytotoxicity of the M170.48 CTL clone against peptide-pulsed T2 cells. Target cells were 51Cr-labeled for 60 min and incubated for 30 min with a range of the indicated peptides. The M170.48 T cell clone was added (E/T ratio = 10:1), and chromium release was then measured after a 4-h incubation period.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2571940&req=5

fig3: Characterization of meloe-derived peptide recognized by the M170.48 T cell clone. (A) Structure of meloe cDNA. Boxes illustrate ORFs >120 bp present along the meloe sequence, and black boxes correspond to ORFs tested for recognition by the CTL clone. (B) M170.48 TNF responses to COS-7 cells (E/T ratio = 1:3) transfected with the indicated plasmids. The T cell clone was added 2 d after the transfection, and the CTL clone reactivity was assessed by a TNF release assay. (C) Nucleotide and amino acid sequences of the ORF 1,230–1,370 of meloe isolated from the M134 cDNA library. The two candidate peptides are bolded. (D) Cytotoxicity of the M170.48 CTL clone against peptide-pulsed T2 cells. Target cells were 51Cr-labeled for 60 min and incubated for 30 min with a range of the indicated peptides. The M170.48 T cell clone was added (E/T ratio = 10:1), and chromium release was then measured after a 4-h incubation period.
Mentions: The meloe cDNA does not contain a long open reading frame (ORF) but multiple short ORFs. ORFs longer than 90 bp are illustrated in Fig. 3 A. The putative ORF described by the NIH Mammalian Gene Collection consortium was located between 486 and 689 bp (21). We tested this ORF and three additional ORFs (Fig. 3 A, black boxes) for recognition by M170.48, after transfection into COS-7 cells, with the HLA-A*0201 cDNA (Fig. 3 B). The ORFs tested (Table II) were chosen on the basis of preliminary results obtained on PCR fragments of meloe (unpublished data).

Bottom Line: Remarkably, the structure of meloe was unusual, with multiple short open reading frames (ORFs).The peptide recognized by the CTL clone was encoded by one of these ORFs, called MELOE-1.Using a specific HLA-A2/peptide tetramer, we showed a correlation between the infusion of TILs containing MELOE-1-specific T cells and relapse prevention in HLA-A2 patients.

View Article: PubMed Central - PubMed

Affiliation: Institut National de Santé et de Recherche Médicale, Unité Mixte de Recherche 892, 44093 Nantes, France.

ABSTRACT
A cytotoxic T lymphocyte (CTL) clone was derived from a tumor-infiltrating lymphocyte (TIL) population infused to a melanoma patient who remained relapse free for 10 yr after this adoptive transfer. This clone recognized all melanoma cell lines tested and, to a lower extent, melanocytes, in the context of human histocompatibility leukocyte antigen A2 (HLA-A2), but it did not recognize other tumor cell types. The gene coding for the antigen recognized by this clone was identified by the screening of a melanoma complementary DNA expression library. This antigen is overexpressed in melanomas, compared with other cancer cell lines and healthy tissues, and was thus called melanoma-overexpressed antigen (meloe). Remarkably, the structure of meloe was unusual, with multiple short open reading frames (ORFs). The peptide recognized by the CTL clone was encoded by one of these ORFs, called MELOE-1. Using a specific HLA-A2/peptide tetramer, we showed a correlation between the infusion of TILs containing MELOE-1-specific T cells and relapse prevention in HLA-A2 patients. Indeed, 5 out of 9 patients who did not relapse were infused with TILs that contained MELOE-1-specific T cells, whereas 0 out of the 21 patients who relapsed was infused with such TIL-containing lymphocytes. Overall, our results suggest that this new antigen is involved in immunosurveillance and, thus, represents an attractive target for immunotherapy protocols of melanoma.

Show MeSH
Related in: MedlinePlus