Antitumor Monoclonal Antibodies Enhance Cross-Presentation of Cellular Antigens and the Generation of Myeloma-specific Killer T Cells by Dendritic Cells
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- Kavita M. Dhodapkar
- 1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, the
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- Joseph Krasovsky
- 1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, the
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- Barbara Williamson
- 3Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan Kettering, New York, NY 10021
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- Madhav V. Dhodapkar
- 1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, the
抄録
<jats:p>The mechanism of antitumor effect of monoclonal antibodies (mAbs) is not fully understood. Here we show that coating myeloma cells with anti–syndecan-1 antibody promotes cross-presentation of cellular antigens by dendritic cells (DCs) to autologous T cells from healthy donors. The tumor cells treated with anti–syndecan-1 or isotype-matched control antibody were fed to HLA-mismatched monocyte-derived immature DCs. Tumor cell–loaded mature DCs induced a strong CD8+ T cell response that was specific for the cancer-testis (C-T) antigens expressed in the tumor. The CD8+ T cells killed peptide-pulsed targets, as well as myeloma tumor cells. Importantly, mAbs-coated tumor-loaded DCs were consistently superior to DCs loaded with peptides or dying cells for eliciting tumor-specific killer T cells. This enhanced cross-presentation was not due to enhanced tumor cell uptake or to DC maturation. When mixtures of NY-Eso-1-positive and -negative myeloma cells were captured by DCs, the anti–syndecan-1 antibody had to be on the NY-Eso-1-positive cells to elicit NY-Eso-1–specific response. Cross-presentation was inhibited by pretreatment of DCs with Fcγ receptor blocking antibodies. Targeting of mAb-coated tumors to DCs may contribute to the efficacy of tumor-reactive mAb and offers a new strategy for immunotherapy.</jats:p>
収録刊行物
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 195 (1), 125-133, 2002-01-07
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1363951795616360320
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- NII論文ID
- 30017416271
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- ISSN
- 15409538
- 00221007
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