title: Bacterial ghosts as adjuvants in syngeneic tumour cell lysate-based anticancer vaccination in a murine lung carcinoma model.
abstract: Instead of relying on external anticancer factors for treatment, immunotherapy utilizes the host's own immune system and directs it against given tumour antigens. This study demonstrated that it is possible to overcome the documented immunosuppressive properties of tumour cell lysate by supplementing it with appropriate adjuvant. Lewis lung carcinoma (LLC)‑challenged C57BL/6 mice were treated with LLC cryo‑lysate mixed with either bacterial ghosts (BGs) generated from E. coli Nissle 1917 or B. subtilis 70 kDa protein as adjuvants. Median and overall survival, the size of metastatic foci in lung tissue and levels of circulating CD8a+ T cells were evaluated and compared to the untreated control mice or mice treated with LLC lysate alone. After primary tumour removal, a course of three subcutaneous vaccinations with LLC lysate supplemented with BGs led to a significant increase in overall survival (80% after 84 days of follow‑up vs. 40% in untreated control mice), a significant increase in circulating CD8a+ T cells (16.57 vs. 12.6% in untreated control mice) and a significant decrease in metastasis foci area and incidence. LLC lysate supplemented with B. subtilis protein also improved the inspected parameters in the treated mice, when compared against the untreated control mice, but not to a significant degree. Therefore, whole cell lysate supplemented with BGs emerges as an immunostimulatory construct with potential clinical applications in cancer treatment.
authors.affiliation: National Cancer Institute, LT-08660 Vilnius, Lithuania.
authors.forename: Jan Aleksander
authors.initials: JA
authors.lastname: Kraśko
authors.affiliation: National Cancer Institute, LT-08660 Vilnius, Lithuania.
authors.forename: Karolina
authors.initials: K
authors.lastname: Žilionytė
authors.affiliation: National Cancer Institute, LT-08660 Vilnius, Lithuania.
authors.forename: Adas
authors.initials: A
authors.lastname: Darinskas
authors.affiliation: National Cancer Institute, LT-08660 Vilnius, Lithuania.
authors.forename: Marius
authors.initials: M
authors.lastname: Strioga
authors.affiliation: Institute of Physiology, BY-220072 Minsk, Republic of Belarus.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Rjabceva
authors.affiliation: Institute of Physiology, BY-220072 Minsk, Republic of Belarus.
authors.forename: Iosif
authors.initials: I
authors.lastname: Zalutsky
authors.affiliation: Institute of Physiology, BY-220072 Minsk, Republic of Belarus.
authors.forename: Marina
authors.initials: M
authors.lastname: Derevyanko
authors.affiliation: Institute of Physiology, BY-220072 Minsk, Republic of Belarus.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kulchitsky
authors.affiliation: BIRD-C GmbH, A-1030 Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Lubitz
authors.affiliation: BIRD-C GmbH, A-1030 Vienna, Austria.
authors.forename: Pavol
authors.initials: P
authors.lastname: Kudela
authors.affiliation: National Cancer Institute, LT-08660 Vilnius, Lithuania.
authors.forename: Edita
authors.initials: E
authors.lastname: Miseikyte-Kaubriene
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, 03022 Kyiv, Ukraine.
authors.forename: Olha
authors.initials: O
authors.lastname: Karaman
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, 03022 Kyiv, Ukraine.
authors.forename: Hennadii
authors.initials: H
authors.lastname: Didenko
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, 03022 Kyiv, Ukraine.
authors.forename: Hryhorii
authors.initials: H
authors.lastname: Potebnya
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, 03022 Kyiv, Ukraine.
authors.forename: Vasyl
authors.initials: V
authors.lastname: Chekhun
authors.affiliation: National Cancer Institute, LT-08660 Vilnius, Lithuania.
authors.forename: Vita
authors.initials: V
authors.lastname: Pašukonienė
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use; D001412:Bacillus subtilis; D001419:Bacteria / Q000737:chemistry / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002457:Cell Extracts / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004926:Escherichia coli; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D002457:Cell Extracts