TY  - JOUR
A1  - Strobel, Sophia
A1  - Machiraju, Devayani
A1  - Hülsmeyer, Ingrid
A1  - Becker, Jürgen C.
A1  - Paschen, Annette
A1  - Jäger, Dirk
A1  - Wels, Winfried
A1  - Bachmann, Michael
A1  - Hassel, Jessica C.
T1  - Expression of potential targets for cell-based therapies on melanoma cells
T2  - Life
N2  - 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.
KW  - melanoma
KW  - target
KW  - HER2
KW  - TRP2
KW  - ABCB5
KW  - gp100
KW  - p53
KW  - GD2
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62137
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-621373
SN  - 2075-1729
N1  - This work was funded by the Joint Funding project grant “UniCAR NK cells” from the German Cancer Consortium (DKTK).
VL  - 11
IS  - 4, art. 269
SP  - 1
EP  - 11
PB  - MDPI
CY  - Basel
ER  -