title: Chlorin e6-mediated photodynamic effect diminishes therapeutic potential of 5-aza-2'-deoxycytidine-based whole-tumour-cell vaccine in mice bearing squamous cell carcinoma SCCVII.
abstract: After years of setbacks, therapeutic cancer vaccines have become an alternative treatment option. Among the diversity of targeted tumour associated antigens (TAA), cancer-testis antigens (CTAs) are promising targets for cancer immunotherapy because they are highly immunogenic; meanwhile, they are expressed in human tumours of different histological origin but not in adult somatic tissues. Epigenetic modifications, such as DNA methylation, regulate CTAs expression both in normal and cancer cells. 5-Aza-2'-deoxycytidine (5-AZA-CdR), a DNA hypomethylating drug, induces the expression of CTAs in neoplastic cells. In these studies, we used 5-AZA-CdR-mediated up-regulation of CTAs and chlorin e6-mediated photodynamic effect in the production of a whole-tumour-cell vaccine against murine squamous cell carcinoma SCCVII in C3H/HeN mice. The results show that 5-AZA-CdR can be used to elevate levels of diverse CTAs in SCCVII cells. The 5-AZA-CdR-based vaccine, combined with the systemic administration of 5-AZA-CdR, delayed tumour growth. However, the treatment had no effect on survival in mice, most likely because of the toxicity of systemic treatment with 5-AZA-CdR. The photodynamic effect diminished therapeutic potential of 5-AZA-CdR-based vaccine. Chemo-immunotherapy with 5-AZA-CdR and therapeutic cancer vaccines may be an alternative approach to cancer therapy. However, further studies are needed to optimize treatment and vaccine preparation protocols.
authors.affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7 Street, Krakow 30-387, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Marczynska
authors.affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7 Street, Krakow 30-387, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Banas
authors.affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7 Street, Krakow 30-387, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Guzik
authors.affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7 Street, Krakow 30-387, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Koltun
authors.affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7 Street, Krakow 30-387, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Majewski
authors.affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7 Street, Krakow 30-387, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Cichy
authors.affiliation: Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7 Street, Krakow 30-387, Poland; Department of Radiation and Cellular Oncology, University of Chicago, MC 0085, 5841 S. Maryland Ave., Chicago, IL 60637, USA.
authors.forename: Martyna
authors.initials: M
authors.lastname: Krzykawska-Serda
authors.affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7 Street, Krakow 30-387, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Makarska
authors.affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7 Street, Krakow 30-387, Poland. Electronic address: kwitniewski@gumed.edu.pl.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kwitniewski
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D019175:DNA Methylation; D000077209:Decitabine; D004797:Enzyme-Linked Immunosorbent Assay; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011166:Porphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D014184:Transplantation, Homologous
chemical_list: D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; D019496:Cancer Vaccines; D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; C062985:phytochlorin; D000077209:Decitabine; D001374:Azacitidine
keywords: Cancer; Cancer–testis antigens; DNA methylation; Immunotherapy; Photodynamic therapy; Vaccine