Mesothelioma and Immune Profile of Pleural Effusions
One interesting study is called, "Regulatory T cells and cytokines in malignant pleural effusions secondary to mesothelioma and carcinoma." Cancer Biol Ther. 2005 Mar;4(3):342-6. Epub 2005 Mar 1 - By DeLong P, Carroll RG, Henry AC, Tanaka T, Ahmad S, Leibowitz MS, Sterman DH, June CH, Albelda SM, Vonderheide RH. - Thoracic Oncology Research Laboratory, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 ' Here is an excerpt: "AbstractImmunotherapy against a variety of malignancies, including pleural-based malignancies, has shown promise in animal models and early human clinical trials, but successful efforts will need to address immunosuppressive factors of the tumor and host, particularly certain cytokines and CD4(+) CD25(+) regulatory T cells (Treg). Here, we evaluated the cellular and cytokine components of malignant pleural effusions from 44 patients with previously diagnosed mesothelioma, non-small cell lung cancer (NSCLC), or breast cancer and found significant differences in the immune profile of pleural effusions secondary to mesothelioma vs. carcinoma. Although a high prevalence of functionally suppressive CD4(+) CD25(+) T cells was found in carcinomatous pleural effusions, mesothelioma pleural effusions contained significantly fewer CD4(+) CD25(+) T cells. Activated CD8(+) T cells in pleural fluid were significantly more prevalent in mesothelioma than carcinoma. However, there is clear patient-to-patient variability and occasional mesothelioma patients with high percentages of CD4(+) CD25(+) pleural effusion T cells and low percentages of CD8(+) CD25(+) pleural effusion T cells can be identified. Mesothelioma pleural effusions contained the highest concentrations of the immunosuppressive cytokine transforming growth factor (TGF)-beta. Thus, the contribution of cellular and cytokine components of immunosuppression associated with malignant pleural effusions varies by tumor histology and by the individual patient. These results have implications for the development of immunotherapy directed to the malignant pleural space, and suggest the need to tailor immunotherapy to overcome immunosuppressive mechanisms in tumor environments."
One interesting study is called, "Malignant fibrosarcomatous mesothelioma and benign pleural fibroma (localized fibrous mesothelioma) in tissue culture: A comparison of the in Vitro pattern of growth in relation to the cell of origin" by E. Alvarez-Fernandez MD, PHD, M. D. Diez-Nau MD ' Cancer Volume 43, Issue 5, pages 1658'1663, May 1979. Here is an excerpt: "Abstract - Two cases of fibrous mesothelioma are presented. The first is a malignant tumor containing bundles of spindle-shaped cells with a dense reticulin network and nests of epithelial-like cells. The second is a benign tumor made up of spindle-shaped cells arranged in bundles with abundant reticulin and collagen fibers. Tissue culture in the first case revealed plaques similar to those formed by epithelial tumors. The second case had a fibroblastic pattern with single isolated spindle-shaped cells. These findings confirmed the mesothelial nature of fibrosarcomatous mesothelioma and supported the view that the so-called localized fibrous mesotheliomas could be fibroblastic neoplasms derived from the submesothelial connective tissue."
One interesting study is called, "Phase I Study of SS1P, a Recombinant Anti-Mesothelin Immunotoxin Given as a Bolus I.V. Infusion to Patients with Mesothelin-Expressing Mesothelioma, Ovarian, and Pancreatic Cancers" by Raffit Hassan, Susie Bullock, Ahalya Premkumar, Robert J. Kreitman, Hedy Kindler Mark C. Willingham and Ira Pastan - Clinical Cancer Research September 2007 13; 5144. Here is an excerpt: "Abstract - Purpose: To determine the toxicities, maximum tolerated dose (MTD) and pharmacokinetics of the recombinant immunotoxin SS1P (anti-mesothelin dsFv-PE38) in patients with mesothelin-expressing cancers. Experimental Design: SS1P given as a 30-min i.v. infusion every other day (QOD) for six or three doses was administered to 34 patients with advanced mesothelioma (n = 20), ovarian (n = 12), and pancreatic (n = 2) cancer. Results: The initial cohort of 17 patients received SS1P QOD × 6 doses and the MTD was 18 μg/kg/dose. Dose-limiting toxicities (DLT) included grade 3 uticaria (one patient) and grade 3 vascular leak syndrome (two patients). To allow further SS1P dose escalation, 17 patients were treated on the QOD × 3 schedule and the MTD was 45 μg/kg/dose. The DLT was grade 3 pleuritis and was seen in two of two patients treated at a dose of 60 μg/kg and in one of nine patients treated at a dose of 45 μg/kg. At the MTD of 45 μg/kg, the mean Cmax of SS1P was 483 ng/mL and half-life was 466 min. Of the 33 evaluable patients treated, 4 had minor responses, 19 had stable disease (including 2 with resolution of ascites), and 10 had progressive disease.
Conclusions: SS1P is well tolerated with pleuritis as the DLT at the highest dose level. Evidence of clinical activity was noted in a group of heavily pretreated patients. Phase II clinical trials of SS1P are being planned for malignant mesothelioma and other mesothelin-expressing malignancies."
About the Author:
Monty Wrobleski is the author of this article. For more information please click on the following links