![]() After seeding on plasticware for 48–72 h, nonadherent cells and contaminant inflammatory cells were gently removed from the culture by multiple washings with PBS. Enzymatically dissociated cells were then washed twice in RPMI 1640 with 10 % fetal bovine serum and maintained in RPMI supplemented with 10 % fetal bovine serum, 200 μg/ml of penicillin and 200 μg/ml of streptomycin at 37 ☌, 5 % CO2 in 75 cm2 tissue culture flasks or Petri dishes (Corning). Briefly, tumor tissue was mechanically minced to portions no larger than 1 to 3 mm3 in an enzyme solution made of 0.14 % collagenase type I (Sigma) and 0.01 % DNase (Sigma, 2000 KU/mg) in RPMI 1640, and incubated in the same solution in a magnetic stirring apparatus for an hour at room temperature. A total of five primary carcinoma cell lines were established after sterile processing of surgical biopsy specimens, as described previously. Our results demonstrate impressive solitomab antitumor activity against carcinosarcoma cell lines and tumor cells in pleural fluid from patients with gynecologic carcinosarcomas.Īll patients signed an informed consent form according to institutional guidelines and approval for this in vitro study was obtained from the institutional review board. In the current study, we have used flow cytometry and q-Real-time-PCR to evaluate EpCAM expression in primary carcinosarcomas cell lines and explored for the first time the potential of solitomab, an EpCAM/CD3 BiTE®, as a novel therapeutic strategy against carcinosarcoma cell lines and un-manipulated malignant tumor cells isolated from malignant pleural fluid of a patient. ![]() Solitomab’s antitumor activity in preclinical EpCAM positive ovarian tumor xenograft models has shown promise. Solitomab acts by engaging resting polyclonal CD8+ and CD4+ T cells for highly potent redirected lysis of target tumor cells that express EpCAM. The discovery of EpCAM (CD326) expression in a number of solid tumors led to the development of Solitomab (MT110, AMG 110) which is an EpCAM/CD3-bispecific single-chain antibody construct. High levels of expression on the cell surface of multiple human carcinomas makes EpCAM an attractive target for immunotherapy. EpCAM is known to play an important role in multiple cell functions including cell migration, cell signaling, differentiation, and proliferation. ![]() It is predominantly expressed in the basolateral and intercellular surface of simple, pseudo-stratified, and transitional epithelia as well as most epithelial tissues in the female genital tract. EpCAM promotes cell adhesion and is expressed at low levels on different various epithelia. ![]() EpCAM, a 39 to 42 kd protein, consists of three domains including an extracellular domain with 2 epidermal growth factor-like repeats, a transmembrane domain, and a short 26 amino acid cytoplasmic domain. Overexpression of epithelial cell adhesion molecule-1 (EpCAM), also known as TROP-1 or TACSTD1, is a known poor prognostic biomarker across a large number of carcinomas and carcinosarcomas. The discovery of novel diagnostic and therapeutic markers against this aggressive subset of gynecological tumors remains a high priority. While CS comprise only a small percentage (i.e., 1 to 5 %) of ovarian and uterine cancers, the overall 5 year survival for ovarian and uterine CS patient remains a dismal 24 % and 36 %, respectively. While the pathogenesis of CS remains under debate, an increasing body of evidence supports the origin of both elements from a common epithelial cell that undergoes sarcomatous dedifferentiation, rather than two independent progenitors. chondrosarcoma, osteosarcoma, rhabdomyosarcoma and liposarcoma). leiomyosarcoma, fibrosarcoma and endometrial stromal sarcoma), or as “heterologous” when they contain mesenchymal components that are physiologically foreign to the primary site (e.g. CS are classified on the basis of the nature of their mesenchymal elements as "homologous" when mesenchymal components differentiate towards tissues physiologically native to the primary site (e.g. Histologically, the carcinomatous component may include endometrioid, serous, clear cell, squamous or mucinous differentiation or may be undifferentiated. ![]() Gynecological carcinosarcomas (CS), also known as Malignant Mixed Mullerian Tumors (MMMT), are rare biphasic tumors that most commonly arise in the uterus and ovaries. ![]()
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