PMID- 9044853
OWN - NLM
STAT- MEDLINE
DCOM- 19970305
LR  - 20221109
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 57
IP  - 4
DP  - 1997 Feb 15
TI  - Analysis of MAGE-3-specific cytolytic T lymphocytes in human leukocyte antigen-A2 
      melanoma patients.
PG  - 735-41
AB  - The MAGE-3 gene is a member of a multigene family that is selectively expressed 
      by subsets of different human tumor types, including malignant melanoma, but not 
      by normal tissues except for testis and placenta. A cytolytic T lymphocyte 
      (CTL)-defined MAGE-3 antigen, corresponding to the MAGE-3 peptide 271-279 
      associated with the human leukocyte antigen (HLA)-A2 molecule, has been recently 
      identified using T lymphocytes from a normal individual stimulated in vitro with 
      peptide-pulsed autologous antigen-presenting cells. Because MAGE-3 is expressed 
      in 76% of metastatic melanomas, the HLA-A2-restricted MAGE-3 antigen should be 
      expressed by approximately 37% of Caucasians bearing a metastatic melanoma tumor, 
      thus representing an attractive candidate for the elicitation of specific CTL 
      immune responses in vivo. In this study, we determined the proportion of HLA-A2+ 
      melanoma patients displaying detectable MAGE-3 peptide 271-279-specific CTL 
      precursors in peripheral blood. Peptide-specific CTL populations were obtained 
      from at least 4 of 11 HLA-A2+ patients. Peptide-specific CTL lines derived from 
      these populations readily lysed HLA-A2-positive target cells that were pulsed 
      with MAGE-3 peptide 271-279 at nanomolar concentrations yet were unable to 
      recognize (as assessed by cytolysis and cytokine production) MAGE-3-expressing 
      autologous or allogeneic HLA-A2-positive melanoma lines. Similarly, the CTL lines 
      failed to recognize MAGE-3-negative HLA-A2-positive tumor lines after 
      transfection with the MAGE-3 gene, although they were able to recognize COS-7 
      cells transfected with MAGE-3. In contrast, HLA-A1-positive melanoma lines 
      transfected with MAGE-3 were efficiently recognized by CTL lines directed against 
      the MAGE-3 peptide 168-176, a known HLA-A1-restricted CTL epitope. These results 
      suggest that the expression level of the MAGE-3 peptide 271-279, unlike that of 
      MAGE-3 peptide 168-176, in melanomas may be too low to allow efficient 
      recognition by specific CTLs. Thus, it appears that despite the presence of CTL 
      precursors against MAGE-3 peptide 271-279 in some HLA-A2+ melanoma patients, the 
      usefulness of this peptide for specific immunotherapy of melanoma may be limited.
FAU - Valmori, D
AU  - Valmori D
AD  - Ludwig Institute for Cancer Research, University of Lausanne, Switzerland.
FAU - Lienard, D
AU  - Lienard D
FAU - Waanders, G
AU  - Waanders G
FAU - Rimoldi, D
AU  - Rimoldi D
FAU - Cerottini, J C
AU  - Cerottini JC
FAU - Romero, P
AU  - Romero P
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (MAGEA3 protein, human)
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antigens, Neoplasm/*immunology
MH  - HLA-A2 Antigen/*immunology
MH  - Humans
MH  - Immunotherapy
MH  - Leukocytes/*immunology
MH  - Melanoma/*immunology/therapy
MH  - Middle Aged
MH  - Neoplasm Proteins/*immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Tumor Cells, Cultured
EDAT- 1997/02/15 00:00
MHDA- 1997/02/15 00:01
CRDT- 1997/02/15 00:00
PHST- 1997/02/15 00:00 [pubmed]
PHST- 1997/02/15 00:01 [medline]
PHST- 1997/02/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1997 Feb 15;57(4):735-41.