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Cancer Immunology, Immunotherapy

, Volume 55, Issue 8, pp 900–909 | Cite as

Photodynamic therapy-generated vaccine for cancer therapy

  • Mladen Korbelik
  • Jinghai Sun
Original Article

Abstract

A target tumor-derived whole cancer cell therapeutic vaccine was developed based on an in vitro pre-treatment by photodynamic therapy (PDT) and was investigated using a poorly immunogenic tumor model. The vaccine was produced by incubating in vitro expanded mouse squamous cell carcinoma SCCVII cells for 1 h with photosensitizer benzoporphyrin derivative (BPD), then exposing to light (690 nm, 1 J/cm2) and finally to a lethal X-ray dose. Treatment of established subcutaneous SCCVII tumors growing in syngeneic C3H/HeN mice with 2x107 PDT-vaccine cells per mouse by a peritumoral injection produced a significant therapeutic effect, including growth retardation, regression and cures. Tumor specificity of this PDT-generated vaccine was demonstrated by its ineffectiveness when prepared from a mismatched tumor cell line. Vaccine cells retrieved from the treatment site at 1 h postinjection were intermixed with dendritic cells (DC), exhibited heat shock protein 70 on their surface, and were opsonized by complement C3. Tumor-draining lymph nodes treated by the PDT-vaccine contained dramatically increased numbers of DC as well as B and T lymphocytes (with enlarged memory phenotype fraction in the latter), while high levels of surface-bound C3 were detectable on DC and to a lesser extent on B cells. The PDT-vaccine produced no therapeutic benefit against tumors growing in C3-deficient hosts. It is suggested that surface expression of heat shock proteins and complement opsonization are the two unique features of PDT-treated cells securing avid immune recognition of vaccinated tumor and the development of a strong and effective antitumor adaptive immune response.

Keywords

Cancer vaccine Photodynamic therapy Verteporfin Heat shock protein 70 Complement C3 

Notes

Acknowledgement

This research is supported by the Canadian Institutes of Health Research grant MPO-12165.

References

  1. 1.
    Arvieux J, Yssel H, Colomb MG (1988) Antigen-bound C3b and C4b enhances antigen-presenting cell function in activation of human T-cell clones. Immunology 65:229–235PubMedGoogle Scholar
  2. 2.
    Asea A (2003) Chaperone-induced signal transduction pathways. Exerc Immunol Rev 9:25–33PubMedGoogle Scholar
  3. 3.
    Bohana-Kashtan O, Ziporen L, Donin L, Kraus S, Fishelson Z (2004) Cell signals transduced by complement 41:583–597Google Scholar
  4. 4.
    Bolzer C, Li G, Issels RD, Multhoff G (1998) Definition of extracellular localized epitopes of Hsp70 involved in an NK immune response. Cell Stress Chaperones 3:6–11CrossRefGoogle Scholar
  5. 5.
    Carroll MC (2004) The complement system in regulation of adaptive immunity. Nat Immunol 5:981–986PubMedCrossRefGoogle Scholar
  6. 6.
    Cecic I, Korbelik M (2002) Mediators of peripheral blood neutrophilia induced by photodynamic therapy of solid tumors. Cancer Lett 183:43–51PubMedCrossRefGoogle Scholar
  7. 7.
    Cecic I, Korbelik M (2005) Deposition of complement proteins on cells treated by photodynamic therapy in vitro. J Environ Pathol Toxicol Oncol 25 (in press)Google Scholar
  8. 8.
    Critchfield JM, Racke MK, Zuniga-Pflucker JC, Cannella B, Raine CS, Goverman J, Lenardo MJ (1994) T cell depletion in high antigen dose therapy of autoimmune encephalomyelitis. Science 263:1139–1143PubMedCrossRefGoogle Scholar
  9. 9.
    Dempsey PW, Allison ME, Akkaraju S, Goodnow CC, Fearon DT (1996) C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science 271:348–350PubMedCrossRefGoogle Scholar
  10. 10.
    Dougherty TJ (2002) An update on photodynamic therapy applications. J Clin Laser Med Surg 20:3–7PubMedCrossRefGoogle Scholar
  11. 11.
    Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q (1998) Photodynamic therapy. J Natl Cancer Inst 90:889–905PubMedCrossRefGoogle Scholar
  12. 12.
    Gollnick SO, Evans SS, Baumann H, Owczarczak B, Maier P, Wang WC, Ungar E, Henderson BW (2003) Role of cytokines in photodynamic therapy-induced local and systemic inflammation. Br J Cancer 88:1772–1779PubMedCrossRefGoogle Scholar
  13. 13.
    Gollnick SO, Vaughan L, Henderson BW (2002) Generation of effective antitumor vaccines using photodynamic therapy. Cancer Res 62:1604–1608PubMedGoogle Scholar
  14. 14.
    Hawlisch H, Wills-Karp M, Karp CL, Köhl J (2004) The anaphylatoxins bridge innate and adaptive immune responses in allergic asthma. Mol Immunol 41:123–131PubMedCrossRefGoogle Scholar
  15. 15.
    Henderson BW, Gollnick SO (2003) Mechanic principles of photodynamic therapy. In: Vo-Dinh T (ed) Biomedical Photonics Handbook. CRC Press, Boca Raton, pp 36-1–36-27Google Scholar
  16. 16.
    Hoos A, Levey DL, Lewis JJ (2004) Autologous heat shock protein-peptide complexes for vaccination against cancer: from bench to bedside. Dev Biol (Basel) 116:109–115Google Scholar
  17. 17.
    Javid B, MacAry PA, Oehlmann W, Singh M, Lehner PJ (2004) Peptides complexed with the protein HSP70 generate efficient human cytolytic T-lymphocyte responses. Biochem Soc Trans 32:622–625PubMedCrossRefGoogle Scholar
  18. 18.
    Korbelik M (2004) The role of Toll-like receptors in photodynamic therapy-elicited host response. Proc SPIE 5319:87–95CrossRefGoogle Scholar
  19. 19.
    Korbelik M, Cecic I (2003) Mechanism of tumor destruction by photodynamic therapy. In: Nalwa HS (ed) Handbook of Photochemistry and Photobiology, vol 4. American Scientific Publishers, Stevenson Ranch, pp 39–77Google Scholar
  20. 20.
    Korbelik M, Dougherty GJ (1999) Photodynamic therapy-mediated immune response against subcutaneous tumors. Cancer Res 59:1941–1946PubMedGoogle Scholar
  21. 21.
    Korbelik M, Krosl G (1995) Accumulation of benzoporphyrin derivative in malignant and host cell populations of the murine RIF tumor. Cancer Lett 97:249–254PubMedCrossRefGoogle Scholar
  22. 22.
    Korbelik M, Krosl G, Krosl J, Dougherty GJ (1999) The role of host lymphoid populations in the response of mouse EMT6 tumor to photodynamic therapy. Cancer Res 56:5647–5652Google Scholar
  23. 23.
    Korbelik M, Sun J, Cecic I (2005) Photodynamic therapy-induced cell surface expression and release of heat shock proteins: relevance for tumor response. Cancer Res 65:1018–1026PubMedGoogle Scholar
  24. 24.
    Lewis JJ (2004) Therapeutic cancer vaccines: using unique antigens. Proc Natl Acad Sci USA 101(Suppl 2):14653–14656PubMedCrossRefGoogle Scholar
  25. 25.
    Mastellos D, Prechl J, László G, Papp K, Oláh E, Argyropoulos E, Franchini S, Tudoran R, Markiewski M, Lambris JD, Erdei A (2004) Novel monoclonal antibodies against mouse C3 interfering with complement activation: description of fine specificity and applications to various immunoassays. Mol Immunol 40:1213–1221PubMedCrossRefGoogle Scholar
  26. 26.
    Morgan BP, Marchbank KJ, Longhi MP, Harris CL, Gallimore AM (2005) Complement: central to innate immunity and bridging to adaptive responses. Immunol Lett 97:171–179PubMedCrossRefGoogle Scholar
  27. 27.
    Prohászka Z, Füst G (2004) Immunological aspects of heat shock proteins—the optimum stress of life. Mol Immunol 41:29–44PubMedCrossRefGoogle Scholar
  28. 28.
    Prohászka Z, Singh M, Nagy K, Lakos G, Duba J, Füst G (2002) Heat shock protein 70 is a potent activator of the human complement system. Cell Stress Chaperones 7:17–22PubMedCrossRefGoogle Scholar
  29. 29.
    Sugiura K, Stock CC (1955) The effect of phosphoramides on the growth of a variety of mouse and rat tumors. Cancer Res 15:38–51PubMedGoogle Scholar
  30. 30.
    Suit HD, Sedlacek RS, Silver G, Dosoretz D (1985) Pentobarbital anesthesia and the response of tumor and normal tissue in the C3Hf/Sed mouse to radiation. Radiat Res 104:47–65PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.British Columbia Cancer AgencyVancouverCanada

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