@article{HaferkampHesbacherWeyandtetal.2014, author = {Haferkamp, Sebastian and Hesbacher, Sonja and Weyandt, Gerhard and Vetter-Kauczok, Claudia S. and Becker, J{\"u}rgen C. and Motschenbacher, Stephanie and Wobser, Marion and Maier, Melissa and Schmid, Corinna P. and Houben, Roland}, title = {p53 regulation by TRP2 is not pervasive in melanoma}, doi = {10.1371/journal.pone.0087440}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111396}, year = {2014}, abstract = {p53 is a central tumor suppressor protein and its inhibition is believed to be a prerequisite for cancer development. In approximately 50\% of all malignancies this is achieved by inactivating mutations in the p53 gene. However, in several cancer entities, including melanoma, p53 mutations are rare. It has been recently proposed that tyrosinase related protein 2 (TRP2), a protein involved in melanin synthesis, may act as suppressor of the p53 pathway in melanoma. To scrutinize this notion we analyzed p53 and TRP2 expression by immunohistochemistry in 172 melanoma tissues and did not find any correlation. Furthermore, we applied three different TRP2 shRNAs to five melanoma cell lines and could not observe a target specific effect of the TRP2 knockdown on either p53 expression nor p53 reporter gene activity. Likewise, ectopic expression of TRP2 in a TRP2 negative melanoma cell line had no impact on p53 expression. In conclusion our data suggest that p53 repression critically controlled by TRP2 is not a general event in melanoma.}, language = {en} } @article{BeckerAndersenHofmeisterMuelleretal.2012, author = {Becker, J{\"u}rgen C. and Andersen, Mads H. and Hofmeister-M{\"u}ller, Valeska and Wobser, Marion and Frey, Lidia and Sandig, Christiane and Walter, Steffen and Singh-Jasuja, Harpreet and K{\"a}mpgen, Eckhart and Opitz, Andreas and Zapatka, Marc and Br{\"o}cker, Eva-B. and thor Straten, Per and Schrama, David and Ugurel, Selma}, title = {Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma}, series = {Cancer Immunology, Immunotherapy}, volume = {61}, journal = {Cancer Immunology, Immunotherapy}, number = {11}, doi = {10.1007/s00262-012-1266-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126215}, pages = {2091-2103}, year = {2012}, abstract = {Background Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets. Patients and methods This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS). Results Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen. Conclusion Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.}, language = {en} } @article{BeckerAndersenHofmeisterMuelleretal.2012, author = {Becker, J{\"u}rgen C. and Andersen, Mads H. and Hofmeister-M{\"u}ller, Valeska and Wobser, Marion and Frey, Lidia and Sandig, Christiane and Walter, Steffen and Singh-Jasuja, Harpreet and K{\"a}mpgen, Eckhart and Opitz, Andreas and Zapatka, Marc and Br{\"o}cker, Eva-B. and thor Straten, Per and Schrama, David and Ugurel, Selma}, title = {Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma}, series = {Cancer Immunology, Immunotherapy}, volume = {61}, journal = {Cancer Immunology, Immunotherapy}, number = {11}, doi = {10.1007/s00262-012-1266-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124830}, pages = {2091-2103}, year = {2012}, abstract = {Background Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets. Patients and methods This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS). Results Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen. Conclusion Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.}, language = {en} }