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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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Detection of MELOE-1/A2–specific CTLs in TILs infused to relapse-free melanoma patients and analysis of their repertoire diversity. (A) HLA-A2 TIL populations labeled with the A2/MELOE-136-44 tetramer. (top) TILs infused to relapse-free patients. (bottom) TILs infused to patients who relapsed. TILs were coincubated with MELOE-1 tetramer and anti-CD8 mAb. Values indicate the percentage of tetramer-positive cells among CD8+ TILs. (B) Repertoire diversity of multimer-sorted populations was evaluated by labeling with 25 anti-Vβ mAbs. Insets illustrate the purity of each sorted TIL population, assessed by MELOE-1–specific tetramer labeling.
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fig5: Detection of MELOE-1/A2–specific CTLs in TILs infused to relapse-free melanoma patients and analysis of their repertoire diversity. (A) HLA-A2 TIL populations labeled with the A2/MELOE-136-44 tetramer. (top) TILs infused to relapse-free patients. (bottom) TILs infused to patients who relapsed. TILs were coincubated with MELOE-1 tetramer and anti-CD8 mAb. Values indicate the percentage of tetramer-positive cells among CD8+ TILs. (B) Repertoire diversity of multimer-sorted populations was evaluated by labeling with 25 anti-Vβ mAbs. Insets illustrate the purity of each sorted TIL population, assessed by MELOE-1–specific tetramer labeling.

Mentions: To address the question of the immunogenicity of this new epitope, we used a specific HLA-A2/peptide tetramer to look for the presence of specific lymphocytes among 30 HLA-A2 TIL populations derived from melanoma-invaded lymph nodes. All of those TIL populations had been infused to melanoma patients in an adjuvant setting between the years 1998 and 2002. After this treatment, 21 of these patients relapsed and 9 remained relapse free. Using a specific HLA/peptide tetramer, we detected the presence of MELOE-1/A2–specific T cells in five out of nine TIL populations that had been infused to relapse-free patients, with frequencies ranging from 0.07 to 3.8% among CD8+ TILs (Fig. 5 A, top). In contrast, we did not observe the presence of such T cells among the TILs infused to the 21 HLA-A2 patients who relapsed. An example of 5 out of these 21 negative TIL populations is shown in Fig. 5 A (bottom). These results document the existence of a correlation between the presence of MELOE-1–specific lymphocytes among infused TILs and relapse prevention (P < 0.001), and thus, suggest the potential immunogenicity of this new HLA-A2 melanoma epitope.


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)

Detection of MELOE-1/A2–specific CTLs in TILs infused to relapse-free melanoma patients and analysis of their repertoire diversity. (A) HLA-A2 TIL populations labeled with the A2/MELOE-136-44 tetramer. (top) TILs infused to relapse-free patients. (bottom) TILs infused to patients who relapsed. TILs were coincubated with MELOE-1 tetramer and anti-CD8 mAb. Values indicate the percentage of tetramer-positive cells among CD8+ TILs. (B) Repertoire diversity of multimer-sorted populations was evaluated by labeling with 25 anti-Vβ mAbs. Insets illustrate the purity of each sorted TIL population, assessed by MELOE-1–specific tetramer labeling.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2571940&req=5

fig5: Detection of MELOE-1/A2–specific CTLs in TILs infused to relapse-free melanoma patients and analysis of their repertoire diversity. (A) HLA-A2 TIL populations labeled with the A2/MELOE-136-44 tetramer. (top) TILs infused to relapse-free patients. (bottom) TILs infused to patients who relapsed. TILs were coincubated with MELOE-1 tetramer and anti-CD8 mAb. Values indicate the percentage of tetramer-positive cells among CD8+ TILs. (B) Repertoire diversity of multimer-sorted populations was evaluated by labeling with 25 anti-Vβ mAbs. Insets illustrate the purity of each sorted TIL population, assessed by MELOE-1–specific tetramer labeling.
Mentions: To address the question of the immunogenicity of this new epitope, we used a specific HLA-A2/peptide tetramer to look for the presence of specific lymphocytes among 30 HLA-A2 TIL populations derived from melanoma-invaded lymph nodes. All of those TIL populations had been infused to melanoma patients in an adjuvant setting between the years 1998 and 2002. After this treatment, 21 of these patients relapsed and 9 remained relapse free. Using a specific HLA/peptide tetramer, we detected the presence of MELOE-1/A2–specific T cells in five out of nine TIL populations that had been infused to relapse-free patients, with frequencies ranging from 0.07 to 3.8% among CD8+ TILs (Fig. 5 A, top). In contrast, we did not observe the presence of such T cells among the TILs infused to the 21 HLA-A2 patients who relapsed. An example of 5 out of these 21 negative TIL populations is shown in Fig. 5 A (bottom). These results document the existence of a correlation between the presence of MELOE-1–specific lymphocytes among infused TILs and relapse prevention (P < 0.001), and thus, suggest the potential immunogenicity of this new HLA-A2 melanoma epitope.

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