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 2 x 10(7) 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.
Korbelik
Mladen
M
British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, V5Z 1L3, BC, Canada. mkorbelik@bccrc.ca
Sun
Jinghai
J
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy*; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents; D011166:Porphyrins
D019496:Cancer Vaccines; D003176:Complement C3; D018840:HSP70 Heat-Shock Proteins; D017319:Photosensitizing Agents; D011166:Porphyrins; C504224:benzoporphyrin D