have shown that peripheral blood or draining lymph node lymphocytes taken from 
an HLA-A2 melanoma patient can be cultured in vitro with an HLA-A2 allogeneic 
melanoma, resulting in CTL with specific lytic activity against autologous 
tumor and other allogeneic melanomas bearing HLA-A2 (15). Interestingly, 
reactivity against the allogeneic HLA determinants on the sensitizing HLA-A2 
melanoma does not occur to a significant degree. These data imply that an 
antigen (or antigens) that is restricted by HLA-A2 is shared among patients 
with melanoma. The antigen is also present in melanomas of patients that are 
not HLA-A2 positive, since transfection of the HLA-A2 gene into HLA-A2 
negative melanomas renders them susceptible to lysis by HLA-A2 CTL (16). 
Although CTL have also been generated that kill allogeneic melanomas sharing 
HLA-A3, HLA-A1 , HLA-A11, HLA-A24 , HLA-A31, and HLA-Cw7, the antigen (s) 
presented by HLA-A2 is preferred for vaccine studies since HLA-A2 is expressed 
by 50% of the Caucasian population. At this time the number of distinct 
melanoma antigens presented by HLA-A2 is not known. At least 6 different 
peptide fractions have been eluted from HLA-A2 melanoma cell lines that are 
recognized by HLA-A2 CTL (17). At a recent meeting, Dr. Thierry Boon and 
colleagues reported that two proteins, tyrosinase and a second undefined 10 kd 
protein, contain the peptides that are recognized by the HLA-A2 melanoma- 
specific CTL. Two immunogenic peptide sequences of tyrosinase have been 
identified. The expression of tyrosinase and the 10 kd protein appear to be 
restricted to melanocytes and melanomas. Forty of 40 melanoma cell lines 
examined to date (100%) have been found to express the tyrosinase gene. 
Shared melanoma antigens presented by HLA-A1 (present on 25% of the Caucasian 
population) have also been identified and the gene sequence determined. The 
antigen, MAGE-1, is a normal protein expressed on 40-50% of melanomas and some 
other tumors but not on most normal tissues (18) . Similar to the HLA-A2 system 
described above, HLA-A1 CTL specific for MAGE-1 expressing melanoma will kill 
allogeneic melanomas also expressing HLA-A1 and MAGE-1. At a recent meeting, 
Dr. Boon's group also presented data that a second melanoma-specific antigen 
belonging to the MAGE family (MAGE-3) can be presented by HLA-A1 . MAGE-3 
appears to be present on 60-70% of HLA-A1 melanoma patients. 
An animal model has been described which demonstrates that HLA-A2 CTL 
(generated by coculturing peripheral blood lymphocytes from a HLA-A2 positive 
patient with an HLA-A2 matched allogeneic melanoma) can mediate tumor 
regression in vivo (19) . The CTL developed specific cytolytic activity 
against autologous and HLA-A2 matched allogeneic melanomas but not against the 
allogeneic determinants of the stimulator melanoma cell line. The CTL were 
administered (in combination with low dose IL-2) to nude mice bearing 3, 7, 
10, and 14-day liver metastases of a separate allogeneic HLA-A2 matched 
[724] 
Recombinant DNA Research, Volume 18 
