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Clinical and Vaccine Immunology, January 2009, p. 96-103, Vol. 16, No. 1
1071-412X/09/$08.00+0     doi:10.1128/CVI.00274-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Construction and Characterization of an Attenuated Listeria monocytogenes Strain for Clinical Use in Cancer Immunotherapy{triangledown}

Anu Wallecha,1* Paulo Cesar Maciag,1 Sandra Rivera,1 Yvonne Paterson,2 and Vafa Shahabi1

Research and Development, Advaxis Inc., North Brunswick, New Jersey 08902,1 Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 191042

Received 15 July 2008/ Returned for modification 3 September 2008/ Accepted 13 November 2008

Listeria monocytogenes has been exploited previously as a vaccine vector for the delivery of heterologous proteins such as tumor-specific antigens for active cancer immunotherapy. However, for effective use of live vector in clinics, safety is a major concern. In the present study, we describe an irreversibly attenuated and highly immunogenic L. monocytogenes platform, the L. monocytogenes dal-, dat-, and actA-deleted strain that expresses the human prostate-specific antigen (PSA) using an antibiotic resistance marker-free plasmid (the dal dat {Delta}actA 142 strain expressing PSA). Despite limited in vivo survival, the dal dat {Delta}actA 142 strain was able to elicit efficient immune responses required for tumor clearance. Our results showed that immunization of mice with the dal dat {Delta}actA 142 strain caused the regression of the tumors established by the prostate adenocarcinoma cell line expressing PSA. An evaluation of immunologic potency indicated that the dal dat {Delta}actA 142 strain elicits a high frequency of PSA-specific immune responses. Interestingly, immunization with the dal dat {Delta}actA 142 strain induced significant infiltration of PSA-specific T cells in the intratumoral milieu. Collectively, our data suggest that the dal dat {Delta}actA 142 strain is a safe and potent vector for clinical use and that this platform may be further exploited as a potential candidate to express other single or multiple antigens for cancer immunotherapy.

* Corresponding author. Mailing address: Advaxis Inc., 675 U.S. Highway One, Suite 120, Technology Center of New Jersey, North Brunswick, NJ 08902. Phone: 91-732-545-1590, ext. 3202. Fax: 91-732-545-1591. E-mail: wallecha{at}advaxis.com

{triangledown} Published ahead of print on 19 November 2008.

Clinical and Vaccine Immunology, January 2009, p. 96-103, Vol. 16, No. 1
1071-412X/09/$08.00+0     doi:10.1128/CVI.00274-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sleator, R. D., Watson, D., Hill, C., Gahan, C. G. M. (2009). The interaction between Listeria monocytogenes and the host gastrointestinal tract. Microbiology 155: 2463-2475 [Abstract] [Full Text]  


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