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The Human Cancer Antigen Mesothelin Is More Efficiently Presented to the Mouse Immune System when Targeted to the DEC‐205/CD205 Receptor on Dendritic Cells
Author(s) -
Wang Bei,
Kuroiwa Janelle M.Y.,
He LiZhen,
Charalambous Anna,
Keler Tibor,
Steinman Ralph M.
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.04933.x
Subject(s) - mesothelin , antigen , immune system , cancer research , epitope , antibody , cd8 , cytokine , immunology , t cell , biology
To develop a tumor vaccine directly targeting tumor antigen to dendritic cells in situ , we engineered human mesothelin (MSLN) into an antibody specific for mouse DEC‐205, a receptor for antigen presentation. We then characterized both T cell and humoral responses to human MSLN and compared immunizing efficacy of DEC‐205‐targeted MSLN to nontargeted protein after a single‐dose immunization. Targeting human MSLN to DEC‐205 receptor induced stronger CD4 + T‐cell responses compared to high doses of mesothelin protein. Approximately 0.5% CD4 + T cells were primed to produce IFN‐γ, tumor necrosis factor‐α, and IL‐2 via intracellular cytokine staining, and the T cells also could proliferate rapidly. The immune response exhibited breadth because the primed CD4 + T cells responded to at least three epitopes in the H‐2 b background. Targeting MSLN protein to DEC‐205 receptor also resulted in cross‐presentation to CD8 + T cells. Antibody responses against human MSLN were also detected in serum from primed mice by ELISA assays. In summary, targeting of MSLN to DEC‐205 improves the induction of CD4 + and CD8 + T‐cell immunity accompanied by an antibody response. DEC‐205‐targeting could be valuable for enhancing immunity to MSLN in cancers where this nonmutated protein is expressed.