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Listeria-derived ActA is an effective adjuvant for primary and metastatic tumor immunotherapy

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Abstract

Tumor immunotherapy is currently at the cusp of becoming an important aspect of comprehensive cancer treatment in the clinic. However, the need for improved adjuvants to augment immune responses against tumor antigens is always present. In this paper, we characterize the Listeria monocytogenes-derived actin-nucleating protein, ActA, as a novel adjuvant for use in tumor immunotherapy. ActA is a virulence factor that is expressed on the cell surface of L. monocytogenes and facilitates the production of actin tails that propel Listeria throughout the cytosol of an infected host cell. It is believed that this ActA-dependent cytosolic motility allows Listeria to evade adaptive host cell defenses and facilitates its invasion into a proximal uninfected host cell. However, there is evidence that ActA fused to a tumor antigen and delivered by L. monocytogenes can perform a beneficial function in tumor immunotherapy as an adjuvant. Our investigation of this adjuvant activity demonstrates that ActA, either fused to or administered as a mixture with a tumor antigen, can augment anti-tumor immune responses, break immune tolerance and facilitate tumor eradication, which suggests that ActA is not only an effective adjuvant in tumor immunotherapy but can also be applied in a number of therapeutic settings.

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Acknowledgments

This work was supported by grant number CA69632 from the National Institutes of Health. Laurence Wood was supported in part by the NIH/NCI-sponsored program T32 CA09140, Training Program in Immunobiology of Normal and Neoplastic Lymphocytes.

Conflict of interest statement

Yvonne Paterson wishes to disclose that she has a financial interest in Advaxis, a vaccine and therapeutic company that has licensed or has an option to license all patents from the University of Pennsylvania that concern the use of Listeria monocytogenes or listerial products as vaccines.

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Authors and Affiliations

  1. Department of Microbiology, University of Pennsylvania, 323 Johnson Pavilion, Philadelphia, PA, 19104, USA

    Laurence M. Wood, Zhen-Kun Pan & Yvonne Paterson

  2. Advaxis Inc., The Technology Centre of New Jersey, Suite 117, 675 U.S. Route 1, North Brunswick, NJ, 08902, USA

    Vafa Shahabi

Authors
  1. Laurence M. Wood
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  2. Zhen-Kun Pan
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  3. Vafa Shahabi
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  4. Yvonne Paterson
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Corresponding author

Correspondence to Yvonne Paterson.

Additional information

L. M. Wood and Z.-K. Pan contributed equally to this manuscript.

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Wood, L.M., Pan, ZK., Shahabi, V. et al. Listeria-derived ActA is an effective adjuvant for primary and metastatic tumor immunotherapy. Cancer Immunol Immunother 59, 1049–1058 (2010). https://doi.org/10.1007/s00262-010-0830-4

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  • DOI: https://doi.org/10.1007/s00262-010-0830-4

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