Mesothelin-based Vaccine Slows Growth of Pancreatic Tumors

Cancer researchers have found that the protein mesothelin was overexpressed in pancreatic cancer and that a vaccine against it slowed tumor growth.

Mesothelin is a 40-kDa protein present on normal mesothelial cells and overexpressed in several human tumors, including mesothelioma and ovarian and pancreatic adenocarcinoma. The mesothelin gene encodes a precursor protein that is processed to yield mesothelin, which is attached to the cell membrane by a glycosylphosphatidyl inositol linkage and a 31-kDa shed-fragment named megakaryocyte-potentiating factor (MPF). Although it has been proposed that mesothelin is related to cell adhesion, the biological function of mesothelin is not known.

In the current study, investigators at the Baylor College of Medicine (Houston, TX, USA) studied the effects of mesothelin overexpression in pancreatic cancer-cell proliferation and migration in vitro and pancreatic cancer progression in vivo. They reported in the February 2008 issue of the journal Molecular Cancer Therapeutics that expression of mesothelin significantly increased tumor cell proliferation and migration by 90% and 300%, respectively, and increased tumor volume fourfold in a nude mice xenograft model when compared with the vector control cell line.
The investigators employed virus-like particles coated with mesothelin as a vaccine to stimulate the immune system of the tumor-bearing mice to recognize and attack the protein. They found that after a series of injections, tumor growth slowed and in some cases the tumor disappeared. The average life span for the untreated mice was four weeks while the immunized mice survived for more than five weeks longer.

"We saw this molecule as very significant in the life of the tumor cells,” explained senior author Dr. Qizhi Yao, professor of surgery at the Baylor College of Medicine. "Our next step was to identify whether this would be a good active immunotherapy target. If we will be able to see the same results in humans, this would allow us to incorporate a combination therapy to treat the tumor. Treatment with a single drug is not effective.”


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Baylor College of Medicine