title: Dendritic cells transfected with tumor RNA for the induction of antitumor CTL in colorectal cancer.
abstract: Dendritic cells (DC) are the most potent antigen-presenting cells known, currently tested for vaccination studies in cancer patients. The use of tumor-derived RNA to load DC overcomes the requirement of defined HLA types and the identification of tumor antigens expressed by the tumors. Here, we show that human monocyte-derived DC generated under serum-free conditions by GM-CSF, IL-4 and TNF-alpha acquire a mature phenotype and expression of the chemokine receptor CCR-7, which plays a pivotal role in DC migration to the afferent lymph nodes. We demonstrate the feasibility of total RNA transfection into such DC using the renal cell carcinoma (RCC) cell line N43-EGFP, which was stably transfected with an EGFP-encoding vector. Moreover, we show that DC transfected with RNA from colorectal cancer cells present HLA class I-restricted antigenic epitopes to induce a primary antitumor CTL response in vitro. Interestingly, the CTL induced by SW480 RNA also recognized another colon cancer line, HCT116, and the RCC line A498. Our results confirm the feasibility of total RNA transfection of serum-free generated DC for the induction of CTL against colon cancer and RCC cells, and support the relevance of shared tumor rejection epitopes between colorectal cancer and RCC.
authors.affiliation: Department of Internal Medicine, University of Genova, Genoa, Italy. a.nencioni@gmx.it
authors.forename: Alessio
authors.initials: A
authors.lastname: Nencioni
authors.forename: Martin R
authors.initials: MR
authors.lastname: Müller
authors.forename: Frank
authors.initials: F
authors.lastname: Grünebach
authors.forename: Anna
authors.initials: A
authors.lastname: Garuti
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mingari
authors.forename: Franco
authors.initials: F
authors.lastname: Patrone
authors.forename: Alberto
authors.initials: A
authors.lastname: Ballestrero
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
mesh_terms: D002292:Carcinoma, Renal Cell / Q000276:immunology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology; D012334:RNA, Neoplasm / Q000235:genetics*; D019707:Receptors, Chemokine / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
chemical_list: D012334:RNA, Neoplasm; D019707:Receptors, Chemokine