Basic StudyMonoclonal Antibodies Targeted Against Melanoma and Ovarian Tumors Enhance Dendritic Cell-Mediated Cross-Presentation of Tumor-Associated Antigens and Efficiently Cross-Prime CD8+ T CellsCioca, Daniel Petru*; Deak, Erika*; Cioca, Flavius†; Paunescu, Virgil*Author Information From the *Immunology Department, Timisoara Medical University, Timisoara, Romania; and †CSC Pharmaceuticals Company, Bucharest, Romania. Received for publication April 26, 2005; accepted June 1, 2005. Reprints: Daniel P. Cioca, University of Medicine and Pharmacy “Victor Babes” Timisoara, Immunology Department, Piata Uta Ioan Colonel Martir No. 2, COD 300041 Timisoara, Romania (e-mail: [email protected]). Journal of Immunotherapy: January 2006 - Volume 29 - Issue 1 - p 41-52 doi: 10.1097/01.cji.0000175496.51594.8b Buy Metrics Abstract Dendritic cells (DCs) constitute very attractive vectors for cancer immunotherapy due to their ability to efficiently capture and present tumor antigens, which initiates tumor-directed T-cell responses. Because the initiation of cytotoxic anti-tumor immune responses requires the cross-presentation mechanism, antigen targeting to DCs represents a very important step in the chain of events that constitutes the cross-priming immune process. In the current study, we explored the ability of DCs loaded with antibody-coated melanoma and ovarian carcinoma tumor cells to cross-present tumor antigens to CD8+ T cells and elicit in vitro anti-tumor immune responses. Coating melanoma and ovarian cancer cells with monoclonal antibodies against different surface antigens (CD44, ME491, LFA-3, and CD24) expressed by the tumor cells promoted the cross-presentation of the tumor-associated antigens as MART-1, gp100, tyrosinase, and NY-ESO-1 by DCs to CD8+ T. These tumor antigen-specific CD8+ T-cell populations resulting from the DC-mediated cross-priming process were identified using specific immune tetramers and were a few fold larger than the ones generated using peptide-pulsed or apoptotic tumor cell-loaded DCs. The CD8+ T cells generated by DCs loaded with monoclonal antibody-coated tumor cells were cytotoxic against the primary melanoma and ovarian carcinoma cells. Thus, targeting monoclonal antibody-coated tumor cells to DCs is a novel method that opens new perspectives for immunotherapy strategies. © 2006 Lippincott Williams & Wilkins, Inc.