Generation of effective antitumor vaccines using photodynamic therapy.
Preclinical studies have shown that photodynamic therapy (PDT) of tumors augments the host antitumor immune response. However, the role of the PDT effect on tumor cells as opposed to the host tissues has not been determined. To test the contribution of the direct effects of PDT on tumor cells to the enhanced antitumor response by the host, we examined the immunogenicity of PDT-generated murine tumor cell lysates in a preclinical vaccine model. We found that the PDT-generated tumor cell lysates were potent vaccines and that PDT-generated vaccines are more effective than other modes of creating whole tumor vaccines, i.e., UV or ionizing irradiation, and unlike other traditional vaccines, PDT vaccines do not require coadministration of an adjuvant to be effective. PDT vaccines are tumor specific and appear to induce a cytotoxic T-cell response. We have demonstrated that although both UV and PDT-generated tumor cell lysates are able to induce phenotypic DC maturation, only PDT-generated lysates are able to activate DCs to express IL-12, which is critical to the development of a cellular immune response. Our results show that PDT effects on tumor cells alone are sufficient to generate an antitumor immune response, indicating that the direct tumor effects of PDT play an important role in enhancing that host antitumor immune response. These studies also suggest that in addition to the role of PDT as a therapeutic modality, PDT-generated vaccines may have clinical potential as an adjuvant therapy.
Gollnick
Sandra O
SO
PDT Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. Sandra.Gollnick@roswellpark.org
Vaughan
Lurine
L
Henderson
Barbara W
BW
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010778:Photochemotherapy / Q000379:methods*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays
D019496:Cancer Vaccines; D007371:Interferon-gamma; D017323:Dihematoporphyrin Ether