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Gene Therapy for Antitumor Vaccination

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Gene Therapy of Cancer

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 542))

Summary

Tumor immunotherapy depends on the interactions between the host, the tumor, and the immune system. Recent data suggests that priming of antigen-specific T cells alone may not be adequate for mediating regression of established tumors because of the immune inhibitory influences within the tumor microenvironment. Thus, we developed a recombinant vaccinia virus vector to express single or multiple T cell costimulatory molecules as a vector for local gene therapy in patients with malignant melanoma. This approach is feasible and generated local and systemic tumor immunity and induced objective clinical responses in patients with metastatic disease. This chapter reviews the details and major issues related to using live, replicating, recombinant poxviruses for gene delivery and antitumor vaccination within the tumor microenvironment.

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References

  1. Zippelius, A., Batard, P. Rubio-Godoy, V. Bioley, G. Lienard, F. Lejeune, D. Rimoldi, P. Guillaume, N. Meidenbauer, A. Mackensen, N. Rufer, N. Lubenow, D. Speiser, J. C. Cerottini, P. Romero, and M. J. Pittet. (2004) Effector function of human tumor-specific CD8 T cells in melanoma lesions: a state of local functional tolerance. Cancer Res. 64, 2865–2873.

    Article  PubMed  CAS  Google Scholar 

  2. Frumento, G., T. Piazza, E. Di Carlo, and S. Ferrini. (2006) Targeting tumor-related immunosuppression for cancer immunotherapy. Endocr Metab Immune Disord Drug Targets. 6, 233–237.

    Article  PubMed  Google Scholar 

  3. Gajewski, T. F. (2000) Monitoring specific T-cell responses to melanoma vaccines: ELISPOT, tetramers, and beyond. Clin Diagn Lab Immunol. 7, 141–144.

    PubMed  CAS  Google Scholar 

  4. Kaufman, H., J. Schlom, and J. Kantor. (1991) A recombinant vaccinia virus expressing human carcinoembryonic antigen (CEA). Int J Cancer. 48, 900–907.

    Article  PubMed  CAS  Google Scholar 

  5. McAneny, D., C. A. Ryan, R. M. Beazley, and H. L. Kaufman. (1996) Results of a phase I trial of a recombinant vaccinia virus that expresses carcinoembryonic antigen in patients with advanced colorectal cancer. Ann Surg Oncol. 3, 495–500.

    Article  PubMed  CAS  Google Scholar 

  6. Zang, X., andJ. P. Allison. (2007) The B7 family and cancer therapy: costimulation and coinhibition. Clin Cancer Res. 13, 5271–5279.

    Article  PubMed  CAS  Google Scholar 

  7. 7.Hodge, J., S. Abrams, J. Schlom, and J. Kantor. (1994) Induction of antitumor immunity by recombinant vaccinia viruses expressing B7–1 or B7–2 costimulatory molecules. Cancer Res. 54, 5552–5555.

    PubMed  CAS  Google Scholar 

  8. Horig, H., D. S. Lee, W. Conkright, J. Divito, H. Hasson, M. LaMare, A. Rivera, D. Park, J. Tine, K. Guito, K. W. Tsang, J. Schlom, andH. L. Kaufman. (2000) Phase I clinical trial of a recombinant canarypoxvirus (ALVAC) vaccine expressing human carcinoembryonic antigen and the B7.1 co-stimulatory molecule. Cancer Immunol Immunother. 49, 504–514.

    Article  PubMed  CAS  Google Scholar 

  9. Hodge, J. W., D. W. Grosenbach, A. N. Rad, M. Giuliano, H. Sabzevari, andJ. Schlom. (2001) Enhancing the potency of peptide-pulsed antigen presenting cells by vector-driven hyperexpression of a triad of costimulatory molecules. Vaccine. 19, 3552–3567.

    Article  PubMed  CAS  Google Scholar 

  10. Hodge, J. W., J. W. Greiner, K. Y. Tsang, H. Sabzevari, C. Kudo-Saito, D. W. Grosenbach, J. L. Gulley, P. M. Arlen, J. L. Marshall, D. Panicali, andJ. Schlom. (2006) Costimulatory molecules as adjuvants for immunotherapy. Front Biosci. 11, 788–803.

    Article  PubMed  CAS  Google Scholar 

  11. Kaufman, H. L., S. Kim-Schulze, K. Manson, G. Deraffele, J. Mitcham, K. S. Seo, D. W. Kim, andJ. Marshall. (2007) Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer. J Transl Med. 5, 60.

    Article  PubMed  Google Scholar 

  12. Hodge, J. W., H. Sabzevari, A. G. Yafal, L. Gritz, M. G. Lorenz, and J. Schlom. (1999) A triad of costimulatory molecules synergize to amplify T-cell activation. Cancer Res. 59, 5800–5807.

    PubMed  CAS  Google Scholar 

  13. Marshall, J. L., R. J. Hoyer, M. A. Toomey, K. Faraguna, P. Chang, E. Richmond, J.E. Pedicano, E. Gehan, R. A. Peck, P. Arlen, K. Y. Tsang, and J. Schlom. (2000) Phase I study in advanced cancer patients of a diversified prime-and-boost vaccination protocol using recombinant vaccinia virus and recombinant nonreplicating avipox virus to elicit anti-carcinoembryonic antigen immune responses. J Clin Oncol. 18, 3964–3973.

    PubMed  CAS  Google Scholar 

  14. Tirapu, I., E. Huarte, C. Guiducci, A. Arina, M. Zaratiegui, O. Murillo, A. Gonzalez, C. Berasain, P. Berraondo, P. Fortes, J. Prieto, M. P. Colombo, L. Chen, andI. Melero. (2006) Low surface expression of B7–1 (CD80) is an immunoescape mechanism of colon carcinoma. Cancer Res. 66, 2442–2450.

    Article  PubMed  CAS  Google Scholar 

  15. Kaufman, H. L., G. DeRaffele, J. Mitcham, D. Moroziewicz, S. M. Cohen, K. S. Hurst-Wicker, K. Cheung, D. S. Lee, J. Divito, M. Voulo, J. Donovan, K. Dolan, K. Manson, D. Panicali, E. Wang, H. Hörig, and F. M. Marincola. (2005) Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma. J Clin Invest. 115, 1903–-1912.

    Article  PubMed  CAS  Google Scholar 

  16. Kaufman, H. L., S. Cohen, K. Cheung, G. DeRaffele, J. Mitcham, D. Moroziewicz, J. Schlom, and C. Hesdorffer. (2006) Local delivery of vaccinia virus expressing multiple costimulatory molecules for the treatment of established tumors. Hum Gene Ther. 17, 239–244.

    Article  PubMed  CAS  Google Scholar 

  17. Kaufman, H. L., W. Conkright, J. Divito, H. Horig, R. Kaleya, D. Lee, S. Mani, D. Panicali, L. Rajdev, T. S. Ravikumar, S. Wise-Campbell, and M. J. Surhland. (2000) A phase I trial of intra lesional RV-B7.1 vaccine in the treatment of malignant melanoma. Hum Gene Ther. 11, 1065–1082.

    Article  PubMed  CAS  Google Scholar 

  18. Kaufman, H. L., G. DeRaffele, J. Divito, H. Horig, D. Lee, D. Panicali, andM. Voulo. (2001) A phase I trial of intralesional rV-Tricom vaccine in the treatment of malignant melanoma. Hum Gene Ther. 12, 1459–1480.

    Article  PubMed  CAS  Google Scholar 

  19. Panelli, M. C., E. Wang, G. Phan, M. Puhlmann, L. Miller, G. A. Ohnmacht, H. G. Klein, andF. M. Marincola. (2002) Gene-expression profiling of the response of peripheral blood mononuclear cells and melanoma metastases to systemic IL-2 administration. Genome Biol 3, RESEARCH0035.

    Article  PubMed  Google Scholar 

  20. Panelli, M. C., E. Wang, V. Monsurro, and F. M. Marincola. (2002) The role of quantitative PCR for the immune monitoring of cancer patients. Expert Opin Biol Ther. 2, 557–564.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Bret Taback, Gail DeRaffele, RN, and Josephine Mitcham for clinical and data management support; and Dae Won Kim and Dorota Moroziewicz for technical assistance. This work was supported by National Institutes of Health (NIH) grant RO1 CA093696.

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Authors and Affiliations

  1. The Tumor Immunology Laboratory, Division of Surgical Oncology, Columbia University, New York, USA

    Seunghee Kim-Schulze & Howard L. Kaufman

Authors
  1. Seunghee Kim-Schulze
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  2. Howard L. Kaufman
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Editor information

Editors and Affiliations

  1. Molecular Medicine (MDC), Max Delbrück Center for, Robert-Rössle-Str. 10, Berlin, 13125, Germany

    Wolfgang Walther

  2. Molecular Medicine (MDC), Max Delbrück Center for, Robert-Rössle-Str. 10, Berlin, 13125, Germany

    Ulrike S. Stein

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Kim-Schulze, S., Kaufman, H.L. (2009). Gene Therapy for Antitumor Vaccination. In: Walther, W., Stein, U. (eds) Gene Therapy of Cancer. Methods in Molecular Biology™, vol 542. Humana Press. https://doi.org/10.1007/978-1-59745-561-9_27

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  • DOI: https://doi.org/10.1007/978-1-59745-561-9_27

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-934115-85-5

  • Online ISBN: 978-1-59745-561-9

  • eBook Packages: Springer Protocols

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