Tumor antigen-specific redirection of cytotoxic T cells (CTLs) or natural killer (NK) cells including
chimeric antigen receptor (CAR-) and
T cell receptor (TCR-)
cell therapy is currently being evaluated in different
tumor entities including
melanoma. Expression of
melanoma-specific
antigen recognized by the respective CAR or TCR directly or presented by HLA molecules is an indispensable prerequisite for this
innovative therapy. In this study, we investigated in 168 FFPE
tumor specimens of patients with stage I-IV
melanoma the
protein expression of HER2, TRP2, ABCB5, gp100, p53, and GD2 by immunohistochemistry (IHC). These results were correlated with clinical parameters. Membrane expression of HER2 and GD2 was also investigated in ten
melanoma cell lines by flow cytometry for which corresponding
tumors were analyzed by IHC. Our results demonstrated that gp100 was the most frequently overexpressed
protein (61%), followed by TRP2 (50%), GD2 (38%), p53 (37%), ABCB5 (17%), and HER2 (3%). TRP2 expression was higher in primary
tumors compared to
metastases (p = 0.005). Accordingly, TRP2 and ABCB5 expression was significantly associated with lower
tumor thickness of the primary (p = 0.013 and p = 0.025). There was no association between
protein expression levels and survival in advanced
melanoma patients. Flow cytometric analysis revealed abundant surface expression of GD2 and HER2 in all
melanoma cell lines. The discordant HER2 expression in situ and in vitro suggests a tissue culture associated induction. In summary, our data support the use of gp100 and GD2 as a potential target for developing engineered TCR- or CAR-cell
therapies, respectively, against
melanoma.