作者: Kind, Simon ; Bawahab, Ahmed Abdulwahab ; Weidemann, Sören ; Marx, Andreas ; Möller, Katharina ; Göbel, Cosima ; Perez, Daniel ; Büscheck, Franziska ; Möller-Koop, Christina ; Izbicki, Jakob R. ; Merenkow, Christina ; Fraune, Christoph ; Clauditz, Till S. ; Chirico, Viktoria ; Luebke, Andreas M. ; Hinsch, Andrea ; Wilczak, Waldemar ; Höflmayer, Doris ; Jacobsen, Frank ; Hube-Magg, Claudia ; Sauter, Guido ; Simon, Ronald ; Dum, David

Syndecan-1 (CD138) is a transmembrane proteoglycan known to be expressed in various normal and malignant tissues. It is of interest because of a possible prognostic role of differential expression in tumors and its role as a target for indatuximab, a monoclonal antibody coupled with a cytotoxic agent. To comprehensively analyze CD138 in normal and neoplastic tissues, we used tissue microarrays (TMAs) for analyzing immunohistochemically detectable CD138 expression in 2,518 tissue samples from 85 different tumor entities and 76 different normal tissue types. The data showed that CD138 expression is abundant in tumors. At least an occasional weak CD138 immunostaining could be detected in 71 of 82 (87%) different tumor types, and 58 entities (71%) had at least one tumor with a strong positivity. In normal tissues, a particularly strong expression was found in normal squamous epithelium of various organs, goblet and columnar cells of the gastrointestinal tract, and in hepatocytes. The highly standardized analysis of most human cancer types resulted in a ranking order of tumors according to the frequency and levels of CD138 expression. CD138 immunostaining was highest in squamous cell carcinomas such as from the esophagus (100%), cervix uteri (79.5%), lung (85.7%), vagina (89.7%) or vulva (73.3%), and in invasive urothelial cancer (76.2%). In adenocarcinomas, CD138 was also high in lung (82.9%) and colorectal cancer (85.3%) but often lower in pancreas (73.3%), stomach (54.2% in intestinal type), or prostate carcinomas (16.3%). CD138 expression was usually low or absent in germ cell tumors, sarcomas, endocrine tumors including thyroid cancer, and neuroendocrine tumors. In summary, the preferential expression in squamous cell carcinomas of various sites makes these cancers prime targets for anti-CD138 treatments once these might become available. Abundant expression in many different normal tissues might pose obstacles to exploiting CD138 as a therapeutic target, however.

2019-12-01·Molecular Carcinogenesis2区 · 医学

A shift from membranous and stromal syndecan‐1 (CD138) expression to cytoplasmic CD138 expression is associated with poor prognosis in breast cancer

2区 · 医学

Article

作者: Kind, Simon ; Möller, Katharina ; Weidemann, Sören ; Krech, Till ; Hube‐Magg, Claudia ; von Leffern, Ingo ; von der Assen, Albert ; Müller, Volkmar ; Büscheck, Franziska ; Bawahab, Ahmed Abdulwahab ; Fraune, Christoph ; Hinsch, Andrea ; Simon, Ronald ; Jaretzke, Annika ; Krech, Rainer H. ; Heilenkötter, Uwe ; Möller‐Koop, Christina ; Burandt, Eike ; Witzel, Isabell ; Lebok, Patrick ; Paluchowski, Peter ; Wilke, Christian ; Schmalfeldt, Barbara ; Höflmayer, Doris ; Wilczak, Waldemar ; Dum, David

AbstractSyndecan‐1 (CD138) is a transmembrane proteoglycan expressed in normal and malignant tissues. It is of interest because of a possible prognostic effect in tumors and as a target for Indatuximab, a monoclonal antibody coupled to a cytotoxic agent. To assess the prognostic role of CD138 expression in breast cancer (BCa), a tissue microarray containing 1535 BCa specimens was analyzed by immunohistochemistry. Cytoplasmic, membranous, and stromal CD138 staining was separately analyzed. In normal breast tissue, CD138 staining was limited to epithelial cell membranes. In cancers, membranous staining tended to become weaker or even disappeared (38.3% of cancers with absence of membranous staining) but cytoplasmic and stromal staining newly appeared in 29.7% and 58.1% of cancers. Loss of membranous epithelial CD138 staining as well as presence of cytoplasmic and stromal CD138 positivity were—to a variable degree—associated with high pT, high grade, nodal metastasis, estrogen receptor‐negative, progesterone receptor‐negative, human epidermal growth factor receptor 2+, and poor overall patient survival. A combined analysis of epithelial and stromal CD138 expression revealed a link to overall patient survival (P < .0001) with best prognosis for patients with stromal positivity and absence of cytoplasmic staining, the worst prognosis for cancers with cytoplasmic staining and stromal negativity and intermediate prognosis for patients having either cytoplasmic staining or stromal negativity. In multivariate analyses, CD138 was not independent of established prognostic features. In summary, these data reveal a compartment depending prognostic effect of CD138 expression in BCa with cytoplasmic positivity being linked to aggressive cancer and stromal CD138 being linked to a more favorable prognosis.

2018-03-01·Immunotherapy4区 · 医学

Emerging Immune Targets for the Treatment of Multiple Myeloma

4区 · 医学

Review

作者: McBride, Ali ; Mushtaq, Adeela ; Sohail, Atif ; Tenneti, Pavan ; Warraich, Zabih ; Iftikhar, Ahmad ; Kurtin, Sandra E ; Anwer, Faiz

We reviewed emerging immune strategies for multiple myeloma (MM) therapy excluding US FDA approved drugs. In relapsed refractory MM, isatuximab (anti-CD38) monotherapy achieved overall response (OR) of 24%. Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab. We included seven clinical trials on chimeric antigen receptor (CAR) T cells. CAR T-cell targets include BCMA, CD19, KLC and CD138. A recent experience of CAR T-cell (B-cell maturation antigen) therapy in advanced MM has shown global response of 100%. The future of monoclonal antibodies and adoptive T cells for MM treatment seems promising.

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适应症	最高研发状态	国家/地区	公司	日期
膀胱癌	临床2期	-	Biotest AG	-
膀胱癌	临床2期	比利时	Biotest AG	-
膀胱癌	临床2期	德国	Biotest AG	-
乳腺癌	临床2期	比利时	Biotest AG	-
乳腺癌	临床2期	-	Biotest AG	-
乳腺癌	临床2期	德国	Biotest AG	-
多发性骨髓瘤	临床2期	美国	Biotest AG	-