Immunotherapy of carcinomatous pleuritis and peritonitis targeting phosphoglucose isomerase as a vaccine.

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The progression and metastasis of cancer are controlled by extracellular growth factors and cytokines. PGI (EC 5. 3. 1. 9) is a ubiquitous cytosolic enzyme that catalyzes the second step in glycolysis. Molecular cloning and sequencing have identified PGI as a motility factor. I.e., autocrine motility factor (AMF), also known as and neuroleukin or maturation factors. AMF/PGI is also a multifunctional cytokine that exhibits multifunctional growth factor-like activity via a unique cognate 78 kDa (gp78) seven-transmembrane glycoprotein receptor (autocrine motility factor receptor, AMFR). We have shown that the overexpression of AMF/PGI enhances cell proliferation together with up-regulation of cyclin/cyclin-dependent kinase activities and down-regulation of p27^<Kip1>. Overexpression of AMF/PGI and AMFR has been found in a wide spectrum of malignancies and is associated with cancer progression, metastasis, and angiogenesis.The goal of cancer therapy remains as the long-term eradication of … More tumor cells without adverse effects on normal tissue. Conventional approaches utilizing chemotherapy and radiotherapy are limited by both their toxicity and lack of specificity. In recent years, investigators have carried out several studies designed to evaluate whether human tumor-associated antigens can be exploited as targets for immunotherapy, specifically for human cancer vaccine development A major limitation in immunotherapy studies of human cancer is the general lack of appropriate preclinical models. Clinical studies can be difficult to implement, particularly when a clear understanding of the potential efficacy, limitation, and safety of an immunotherapeutic strategy is not available from relevant animal investigations. In this study, we assessed whether overexpression of PGI in human cancer cells enhances the liver metastasis using a mouse model. We also investigated the intracellular signal transduction pathways of PGI in human cancer cell lines. In vivo, after implantation into the nude mice, control cells produced locally relatively small tumors with no evidence of liver metastasis, whereas PGI-transfected cells produced the large tumors and liver metastases. The data submitted here show that PGI expression significantly contributes to the aggressive phenotype of human cancer. Thus, PGI may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Less