Definition: cancer caused by exposure to asbestos, Mesothelioma, more precisely malignant mesothelioma, is a rare form of cancer that develops from the protective lining that covers many of the body's internal organs, the mesothelium.
The Biotherapy : The Solid Tumor Immunotherapy Section conducts translational research for treatment of mesothelioma and lung cancer.
The Molecular Biology Section carries out research directed at designing, producing, and testing new agents (recombinant immunotoxins) to treat cancer. Recombinant immunotoxins (RIT) are genetically modified forms of Pseudomonas exotoxin A that are targeted to cancer cells by Fv portion of antibodies. Three recombinant immunotoxins that have been developed in the LMB are now in clinical trials. The most advanced of these is moxetumomab pasudotox that targets CD22 on B cell malignancies. It has produced many complete and partial remissions in drug resistant Hairy Cell Leukemia, several in children with ALL and is being evaluated in multi-center trials in other B cell malignancies. A second RIT is named SS1P and is directed at mesothelin expressing cancers, which include mesotheliomas, cholangiocarcinomas and cancers of the lung, ovary and pancreas. SS1P has shown activity in phase 1 trials and is now being evaluated in combination with chemotherapy in mesothelioma patients. Based on information gained in clinical trials, we use protein engineering to make these proteins more useful in patients by increasing their activity, decreasing their side effects and decreasing their immunogenicity so more treatment cycles can be given before antibodies develop.
A major focus of The Solid Tumor Immunotherapy Section is to exploit
the tumor differentiation antigen mesothelin for treatment of mesothelioma.
There are ongoing clinical trials of an anti-mesothelin immunotoxin (SS1P) as
well as an anti-mesothelin monoclonal antibody (MORAb-009) in combination with
chemotherapy for treatment of pleural mesothelioma.
Distinguishing malignant mesothelioma from pulmonary adenocarcinoma: an immuno-histochemical approach using a panel of monoclonal antibodies.
A panel of six monoclonal antibodies (MAbs) was employed to evaluate antigen expression in pulmonary adenocarcinomas and mesotheliomas. Monoclonal anti-human milk fat globulin (HMFG-2), anti-carcinoembryonic antigen (NP-2), anti-epithelial membrane antigen (EMA), anti-cytokeratin (PKK-1), anti-tumor-associated antigen 72 (B72.3), and anti-human myelomonocytic antigen (Leu M-1) antibodies were used to localize their respective antigens in formalin-fixed, paraffin-embedded tumors by using the avidin-biotin-complex immunoperoxidase technique. In all, 28 mesotheliomas obtained from Ohio State University Anatomic Pathology files and from a Southwest Oncology Group (SWOG) protocol were compared to 22 pulmonary adenocarcinomas by using this MAb panel. None of the mesotheliomas demonstrated positive staining with MAbs NP-2 (anti-CEA) or Leu M-1. However, 95% (21/22) of adenocarcinomas stained with one of these two antibodies. Although neither of these two MAbs stained all adenocarcinomas, each antibody demonstrated positive immunostaining in more than 90% of the adenocarcinomas studied. Therefore, MABs NP-2 and Leu M-1 are, individually, quite useful for distinguishing mesothelioma from adenocarcinoma. However, in our study, no single MAb could be used to distinguish these two tumor types in every case. MAb B72.3 stained 91% (20/21) adenocarcinomas but also stained 7% (2/28) of mesotheliomas. MAb HMFG-2 reacted positively with 95% of adenocarcinomas, but also stained 39% of the mesotheliomas, usually in a membranous pattern. MAbs EMA and PKK-1 were not found useful in distinguishing mesothelioma from adenocarcinoma. We conclude that MAbs Leu M-1 and NP-2 were both useful in distinguishing mesothelioma from pulmonary adenocarcinoma in that positive staining was demonstrated in adenocarcinomas and not mesotheliomas.
PMID:
2214794 [PubMed - indexed for MEDLINE]
Mesothelioma risks and causes : Cancer Research UK : CancerHelp UK". Cancerhelp.org.uk. 2010-06-23. Retrieved 2010-08-20.
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