Our results also show low concentrations of an immunotoxin targeting mesothelin is cytotoxic to mesothelin-expressing human tumors by inducing apoptosis.
This large study of the MSLN gene and protein expression in common carcinomas provides data for future investigations that evaluate the utility of mesothelin/megakaryocyte potentiating factor as a potential serum tumor marker or target of immunotoxin-based therapy in human cancers.
Peritoneal injection of the transformed cells produced undifferentiated carcinoma or malignant mixed Mullerian tumor and developed ascites; the tumor cells are focally positive for CA125 and mesothelin.
Mesothelin mRNA expression was confirmed with in situ hybridization in all 4 resected primary PCa tumors and with RT-PCR in 18 of 20 PCa cell lines, whereas mesothelin protein expression was confirmed with immunohistochemistry in all 60 resected primary PCa tissues by Argani et al.
External beam radiation of tumor cells at nontoxic levels was shown to enhance the expression of mesothelin and other accessory molecules, resulting in a modest but statistically significant increase in tumor cell lysis by mesothelin-specific T cells.
Mesothelin expression did not correlate significantly with patient age, tumor site, in vitro drug resistance, or tumor differentiation status (P > 0.10).
Thus, the employment of SCT of HLA-A2 linked to the human mesothelin epitope aa540-549 represents a potential opportunity for the clinical translation of DNA vaccines against human mesothelin-expressing tumors, particularly ovarian cancer cells.
Using quantitative PCR, both mesothelin (MSLN) and PTGS1 (COX1) were significantly increased in FOLR1 overexpressing tumors (p=0.014 and p=0.006 respectively).
Our data indicated that vaccination with DNA vaccine targeting Hmeso could generate potent antitumor effects against mesothelin-expressing tumors through both T cell-mediated immunity as well as antibody-mediated immunity.
Although its value as a tumor marker for diagnosis and prognosis and as a preferred target of immunointervention has been evaluated, there is little information on the growth advantage of MSLN on tumor cells.
The interaction between mesothelin and CA125 may facilitate the implantation and peritoneal spread of tumors by cell adhesion, whereas the detailed nature of this interaction is still unknown.
Mesothelin is a potential new target for cancer immunotherapy because it is present at relatively low levels only in mesothelial cells of pleura, peritoneum, and pericardium of healthy people, but is significantly elevated in a number of tumors, including mesothelioma, ovarian, pancreatic, and lung cancers.
Mesothelin (MSLN) may be the most "dramatic" of the tumor markers, being strongly overexpressed in nearly one-third of human malignancies.The biochemical cause is unclear.
The chemokine receptor CCR2b was thus transduced into mesoCAR T cells using a lentiviral vector, and the modified T cells were used to treat established mesothelin-expressing tumors.
Next, we compared cases according to serum SMRP status and observed that MSLN methylation was significantly higher among tumors from patients testing negative for SMRP (< 1.5nM) versus those that were SMRP positive (P < 0.03).
Importantly, adoptive transfer of P4 CAR-expressing T cells mediated the regression of large, established tumor in the presence of soluble mesothelin in a xenogenic model of human ovarian cancer.
A recombinant immunotoxin against the tumor-associated antigen mesothelin reengineered for high activity, low off-target toxicity, and reduced antigenicity.