Flt3L therapy following localized tumor irradiation generates long-term protective immune response in metastatic lung cancer: Its implication in designing a vaccination strategy

Prabir K. Chakravarty, Chandan Guha, Alan Alfieri, Vivek Beri, Zoya Niazova, Niloy J. Deb, Zuoheng Fan, Elaine K. Thomas, Bhadrasain Vikram

Research output: Contribution to journalArticle

31 Scopus citations

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-γ and TNF-α). 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.

Original languageEnglish (US)
Pages (from-to)245-254
Number of pages10
JournalONCOLOGY
Volume70
Issue number4
DOIs
StatePublished - Oct 1 2006

Keywords

  • Dendritic cells
  • Flt3L
  • Immune response
  • Irradiation
  • Vaccination

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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