Cross-Priming of Naive CD8 T Cells against Melanoma Antigens Using Dendritic Cells Loaded with Killed Allogeneic Melanoma Cells

doi:10.1084/jem.192.11.1535

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Published online 27 November 2000.

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© The Rockefeller University Press, 0022-1007/2000/12/1535/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 11, December 4, 2000 1535-1544

Original Article

Cross-Priming of Naive CD8 T Cells against Melanoma Antigens Using Dendritic Cells Loaded with Killed Allogeneic Melanoma Cells

Frederic Berard^a, Patrick Blanco^a, Jean Davoust^a, Eve-Marie Neidhart-Berard^a, Mahyar Nouri-Shirazi^a, Nicolas Taquet^a, Donata Rimoldi^b, Jean Charles Cerottini^b, Jacques Banchereau^a, and A. Karolina Palucka^a
^a Baylor Institute for Immunology Research, Dallas, Texas 75204
^b Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, University Hospital, CHUV, CH-1011 Lausanne, Switzerland

Correspondence to: A. Karolina Palucka, Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, TX 75204. Tel:214-820-7450 Fax:214-820-4813 E-mail:ak.palucka{at}baylordallas.edu.

The goal of tumor immunotherapy is to elicit immune responsesagainst autologous tumors. It would be highly desirable thatsuch responses include multiple T cell clones against multipletumor antigens. This could be obtained using the antigen presentingcapacity of dendritic cells (DCs) and cross-priming. That is,one could load the DC with tumor lines of any human histocompatibilityleukocyte antigen (HLA) type to elicit T cell responses againstthe autologous tumor. In this study, we show that human DCsderived from monocytes and loaded with killed melanoma cellsprime naive CD45RA⁺CD27⁺CD8⁺ T cells against the four sharedmelanoma antigens: MAGE-3, gp100, tyrosinase, and MART-1. HLA-A201⁺naive T cells primed by DCs loaded with HLA-A201^- melanoma cellsare able to kill several HLA-A201⁺ melanoma targets. CytotoxicT lymphocyte priming towards melanoma antigens is also obtainedwith cells from metastatic melanoma patients. This demonstrationof cross-priming against shared tumor antigens builds the basisfor using allogeneic tumor cell lines to deliver tumor antigensto DCs for vaccination protocols.

Key Words: shared tumor antigens, cross-priming, tumor immunity, tumorvaccine, immunotherapy

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