title: Flt3L therapy following localized tumor irradiation generates long-term protective immune response in metastatic lung cancer: its implication in designing a vaccination strategy.
abstract: Flt3 ligand (Flt3L) therapy that expands dendritic cells in vivo in combination with local tumor radiotherapy (RT) significantly improved survival and induced a long-term tumor-specific immune response in a murine model of Lewis lung carcinoma (3LL). The irradiated tumor cells were able to significantly restimulate the splenocytes of the RT + Flt3L cohort in vitro. The restimulated splenocytes demonstrated increased cytotoxic response, lymphocytic proliferation and elevated levels of Th type I cytokines (IL-2, IL-12, IFN-gamma and TNF-alpha). The combination therapy of RT + Flt3L induced a long-term protective immunity in the disease-free animals. The protective effect was further enhanced when the disease-free animals were vaccinated with irradiated tumor cells. The vaccinated animals had significantly greater protection compared to the nonvaccinated group against subsequent challenge with 3LL cells. Taken together, these results indicate that the release of tumor antigens by irradiated dying tumors and concomitant administration of Flt3L was able to facilitate the generation of a tumor-specific long-term immune response against a poorly immunogenic tumor. This effect was further boosted by vaccination with irradiated tumor cells.
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, New York, NY, USA.
authors.forename: Prabir K
authors.initials: PK
authors.lastname: Chakravarty
authors.forename: Chandan
authors.initials: C
authors.lastname: Guha
authors.forename: Alan
authors.initials: A
authors.lastname: Alfieri
authors.forename: Vivek
authors.initials: V
authors.lastname: Beri
authors.forename: Zoya
authors.initials: Z
authors.lastname: Niazova
authors.forename: Niloy J
authors.initials: NJ
authors.lastname: Deb
authors.forename: Zuoheng
authors.initials: Z
authors.lastname: Fan
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Thomas
authors.forename: Bhadrasain
authors.initials: B
authors.lastname: Vikram
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019496:Cancer Vaccines; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D016207:Cytokines; D008565:Membrane Proteins; C084881:flt3 ligand protein