Dendritic cells efficiently acquire and present an

Authors: Yaling Zhou Julie A McEarchern Edward Howard Gary Pestano Michael L Salgaller Marnix L Bosch

Publish Date: 2003/02/15

Volume: 52, Issue: 7, Pages: 413-422

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Abstract

Active immunotherapy of cancer requires the availability of a source of tumor antigens To date no such antigen associated with lung cancer has been identified We have therefore investigated the ability of dendritic cells DC to capture whole irradiated human lung tumor cells and to present a defined surrogate antigen derived from the ingested tumor cells We also describe an in vitro system using a modified human adenocarcinoma cell line A549M1 that expresses the wellcharacterized immunogenic influenza M1 matrix protein as a surrogate tumor antigen Peripheral blood monocytederived DC when cocultured with sublethally irradiated A549 cells or primary lung tumor cells derived from surgical resection of nonsmall cell carcinoma NSCLC efficiently ingested the tumor cells as determined by flow cytometry analysis and confocal microscopic examination More importantly DC loaded with irradiated A549M1 cells efficiently processed and presented tumor cellderived M1 antigen to T cells and elicited antigenspecific immune responses that included IFNγ release from an M1specific Tcell line expansion of M1 peptidespecific Vβ17+ and CD8+ peripheral T cells and generation of M1specific cytotoxic T lymphocytes CTL We also compared DC loaded with irradiated tumor cells to those loaded with tumor cell lysate or killed tumor cells and found that irradiated lung tumor cells as a source of tumor antigen for DC loading is superior to tumor cell lysate or killed tumor cells in efficient induction of antigenspecific Tcell responses Our results demonstrate the feasibility of using lung tumor cellloaded DC to induce immune responses against lung cancerassociated antigens and support ongoing efforts to develop a DCbased lung cancer vaccineWe thank Michael D Roth and Sylvia M Kiertscher and their colleagues at the UCLA School of Medicine for development of the lung tumor cell isolation procedure and for provision of primary NSCLC tissue We also thank Robert Bader for his assistance with cytokine assays

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