Photodynamic therapy-generated vaccine for cancer therapy
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.
KeywordsCancer vaccine Photodynamic therapy Verteporfin Heat shock protein 70 Complement C3
This research is supported by the Canadian Institutes of Health Research grant MPO-12165.
- 3.Bohana-Kashtan O, Ziporen L, Donin L, Kraus S, Fishelson Z (2004) Cell signals transduced by complement 41:583–597Google Scholar
- 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
- 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.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
- 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
- 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
- 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