Antitumor monoclonal antibodies enhance cross-presentation of cellular antigens and the generation of myeloma-specific killer T cells by dendritic cells Journal Article
| Authors: | Dhodapkar, K. M.; Krasovsky, J.; Williamson, B.; Dhodapkar, M. V. |
| Article Title: | Antitumor monoclonal antibodies enhance cross-presentation of cellular antigens and the generation of myeloma-specific killer T cells by dendritic cells |
| Abstract: | 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. |
| Keywords: | unclassified drug; human cell; antigen expression; t lymphocyte; t-lymphocytes; proteins; cancer immunotherapy; apoptosis; multiple myeloma; cell maturation; dendritic cell; neoplasm proteins; membrane proteins; tumor antigen; monoclonal antibody; antigen presentation; dendritic cells; antibodies, monoclonal; immunotherapy; antigens, neoplasm; membrane glycoproteins; tumor cell; testicular neoplasms; tumor immunity; fc receptor; receptors, igg; cell stimulation; antibodies, neoplasm; myeloma; cancer antibody; cancer-testis antigens; interferon type ii; fc receptors; proteoglycans; killer cell; syndecans; humans; human; male; priority journal; article; cell antigen; killer cells; syndecan antibody |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 195 |
| Issue: | 1 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2002-01-07 |
| Start Page: | 125 |
| End Page: | 133 |
| Language: | English |
| DOI: | 10.1084/jem.20011097 |
| PUBMED: | 11781371 |
| PROVIDER: | scopus |
| PMCID: | PMC2196013 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
