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What is needed for effective antitumor immunotherapy? Lessons learned using Listeria monocytogenes as a live vector for HPV-associated tumors

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Abstract

As a vaccine vector, Listeria monocytogenes targets the innate immune system, resulting in a cytokine response that enhances antigen-presenting cell function as well as inducing a Th1 profile. It also enhances cell-mediated immunity by targeting antigen delivery in antigen-presenting cells to both the MHC class I pathway of exogenous presentation that activates CD8 T cells and the MHC class II pathway that processes antigen endogenously and presents it to CD4 T cells. In this review, we describe the development of vaccine constructs that target the human papillomavirus 16 (HPV-16) E7 antigen, and we characterize their effects on tumor regression as well as various immune parameters both innate and adaptive. In particular, we describe the effect on tumor angiogenesis, induction of antitumor suppressor factors like CD4+CD25+ T cells and regulatory cytokines TGF-β and IL-10, homing and infiltration of antigen-specific CD8+ T cells to the tumor, and also effects of the vaccines on antigen-presenting cells, especially focusing on dendritic cell maturation and ability to influence tumor regression. We believe that the identification of several immune parameters that correlate with antitumor efficacy, and of some that have a negative correlation, may have wider application for other cancer immunotherapeutic approaches.

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Acknowledgements

This work was supported by NIH Grant CA 69632 and ACS Grant TURSG LIB-01-168-01. We wish to thank past and current members of the Paterson laboratory, including Gregory Beatty, Mary Dominiecki, George Gunn, Zhen-Kun Pan, John Pappas, Duane Sewell, and Vafa Shahabi, for permission to describe their as-yet-unpublished results.

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Authors and Affiliations

  1. Department of Microbiology, University of Pennsylvania School of Medicine, 323 Johnson Pavilion, 36th St. and Hamilton Walk, Philadelphia, PA, 19104-6076, USA

    S. Farzana Hussain & Yvonne Paterson

Authors
  1. S. Farzana Hussain
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  2. Yvonne Paterson
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Correspondence to Yvonne Paterson.

Additional information

This article is a symposium paper from the second international conference “Strategies for Immune Therapy,” 29 February–3 March 2004, Würzburg, Germany; summarized by G. Pawelec and C. Gouttefangeas.

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Hussain, S.F., Paterson, Y. What is needed for effective antitumor immunotherapy? Lessons learned using Listeria monocytogenes as a live vector for HPV-associated tumors. Cancer Immunol Immunother 54, 577–586 (2005). https://doi.org/10.1007/s00262-004-0600-2

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  • DOI: https://doi.org/10.1007/s00262-004-0600-2

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