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May 02, 2013
 |  BC Innovations  |  Targets & Mechanisms

Add radioactivity to the Listeria

An Albert Einstein College of Medicine of Yeshiva University team has used radiolabeled Listeria monocytogenes to efficiently treat metastatic pancreatic cancer in mice.1 Future studies could involve comparing or combining the strategy with existing nonradioactive immunotherapies that utilize the bacterium as a vector.

L. monocytogenes is a food-borne pathogen that can infect a range of mammalian cell types and cause potentially fatal illness (listeriosis) in immune-compromised individuals. For the last decade, attenuated strains of the bacterium have served as vectors for delivering antigens with high specificity to dendritic cells, thereby eliciting an immune response to cancer or infection.2

At least two companies-Advaxis Inc. and Aduro BioTech Inc.-have vaccines or immunotherapies based on attenuated L. monocytogenes in development to treat various cancers and infectious diseases.

Another advantage of the bacterium is that it survives longer-and thus replicates to a greater extent-in the immunosuppressive environment of tumors than in normal tissues. This has allowed it to be used for cancer imaging in animal models3 and for expressing enzymes capable of converting chemotherapy prodrugs into active therapeutic agents in human breast cancer and mouse melanoma cell lines.4

Moreover, a 2009 study co-led by Claudia Gravekamp and Yvonne Paterson showed that an attenuated L. monocytogenes itself had efficacy in cancer. The bacterium decreased primary and metastatic tumor growth in mouse models for breast cancer almost as effectively as the same bacterial vector expressing a cancer antigen.5

Gravekamp is associate professor of microbiology and immunology at Albert Einstein College of Medicine. Paterson is professor of microbiology at the University of Pennsylvania, professor of nursing and associate dean for research at the University of Pennsylvania's School of Nursing and cofounder of Advaxis.

Those 2009 findings prompted...

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