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PubMed · 15128763

Shift from systemic to site-specific memory by tumor-targeted IL-2.

David Schrama·Rong Xiang·Andreas O Eggert·Mads Hald Andersen·Lars Østergaard Pedersen Ls·Eckhart Kämpgen·Ton N Schumacher·Ralph R Reisfeld·Jürgen C Becker
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Abstract

IL-2 has been approved for treatment of patients with cancer. Moreover, it has been used as a component of vaccines against cancer. In this regard, we have recently demonstrated that dendritic cell-based peptide vaccination in mice required IL-2 to mount an effective immune response against established melanoma metastases. In this study, we confirm this observation by use of tumor-targeted IL-2. However, the development of a protective systemic memory was substantially impaired by this measure, i.e., mice, which successfully rejected s.c. tumors of B16 melanoma after vaccination with dendritic cells pulsed with tyrosinase-related protein 2-derived peptides plus a boost with targeted IL-2, failed to reject a rechallenge with experimental pulmonary metastases. Detailed analysis revealed a change in the distribution of the tumor-reactive T cell population: although targeted IL-2 expanded the local effector population, tyrosinase-related protein 2-reactive T cells were almost completely depleted from lymphatic tissues.

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AnimalsCell Line, TumorCells, CulturedDendritic CellsGrowth InhibitorsHumansImmunologic MemoryImmunotherapy, AdoptiveInterleukin-2Intramolecular OxidoreductasesLung NeoplasmsLymph NodesLymphocyte ActivationLymphocyte DepletionMelanoma, ExperimentalMiceMice, Inbred C57BLOrgan SpecificitySkin NeoplasmsT-Lymphocyte SubsetsVaccines, SubunitJournal ArticleResearch Support, Non-U.S. Gov't

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David Schrama, Rong Xiang, Andreas O Eggert, Mads Hald Andersen, Lars Østergaard Pedersen Ls, Eckhart Kämpgen, Ton N Schumacher, Ralph R Reisfeld, Jürgen C Becker. 2004-05-15. Shift from systemic to site-specific memory by tumor-targeted IL-2.. https://doi.org/10.4049/jimmunol.172.10.5843

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