Cancer immunotherapy using Listeria monocytogenes and listerial virulence factors
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Cancer immunotherapy using Listeria monocytogenes and listerial virulence factors Laurence M. Wood · Patrick D. Guirnalda · Matthew M. Seavey · Yvonne Paterson
Published online: 19 November 2008 © Springer Science+Business Media, LLC 2008
Abstract Our laboratory is interested in how immunogenicity may be modulated in vivo in order to better design more eVective immunotherapeutics against cancer. Our main approach is to use a facultative intracellular bacterium, Listeria monocytogenes, which has the unusual ability to live and grow in the cytoplasm of the cell and is thus an excellent vector for targeting passenger antigens to the major histocompatibility complex (MHC) class I pathway of antigen processing with the generation of authentic CTL epitopes. We have used this approach to target tumor antigens expressed on breast, melanoma and cervical cancer. We are also exploring the role of Listerial virulence factors in potentiating adaptive immune responses by activating innate immunity. SpeciWcally, we are using these proteins as adjuvants for B cell lymphomas. Keywords Listeria monocytogenes · HPV · Her-2/neu · Tumor immunotherapy · Tumor vasculature · Vaccines · Antigen processing · Cell-mediated immunity
Introduction Our laboratory has long been interested in the properties of proteins that render them immunogenic and how such immunogenicity may be modulated in vivo. In the case of the immunoglobulin receptor on B cells both the antigenic site on the protein antigen and the binding site of the immunoglobulin are topographic surfaces. However, in the case of the T cell receptor the antigenic region of the protein is a peptide derived by cellular processing which is expressed on the surface of an antigen presenting cell associated with a molecule
Laurence M. Wood, Patrick D. Guirnalda, Matthew M. Seavey are made an equal contribution to this work. L. M. Wood · P. D. Guirnalda · M. M. Seavey · Y. Paterson (&) Department of Microbiology, University of Pennsylvania School of Medicine, 323 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104-6076, USA e-mail: [email protected]
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of the major histocompatibility complex (MHC). The cellular compartment in which the T cell epitope is generated determines whether it emerges at the cell surface bound to MHC class I or II molecules and, therefore, what type of T cell response is elicited. There have been enormous advances made in the last few years in our understanding of the molecular and cellular machinery that governs the presentation of antigens to the immune system. In our laboratory, we are attempting to apply this knowledge to the development of strategies of immune regulation for cancer. Our work serves two purposes. The Wrst is that we believe that we can learn much about the mechanisms of immunity in testing current theories by manipulating immunopathological states. The second is to heed Albert Sabin’s maxim “To yield to every whim of curiosity, and to allow our passion for inquiry to be restrained by nothing but
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