Expression of potential targets for cell-based therapies on melanoma cells

  • 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.

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Author:Sophia Strobel, Devayani Machiraju, Ingrid Hülsmeyer, Jürgen C. Becker, Annette Paschen, Dirk Jäger, Winfried S. Wels, Michael Bachmann, Jessica C. Hassel
Parent Title (English):Life
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/03/24
Date of first Publication:2021/03/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/10/19
Tag:ABCB5; GD2; HER2; TRP2; gp100; melanoma; p53; target
Issue:4, art. 269
Page Number:11
First Page:1
Last Page:11
This work was funded by the Joint Funding project grant “UniCAR NK cells” from the German Cancer Consortium (DKTK).
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0