PMID- 18481381 OWN - NLM STAT- MEDLINE DCOM- 20080612 LR - 20181201 IS - 1524-9557 (Print) IS - 1524-9557 (Linking) VI - 31 IP - 2 DP - 2008 Feb-Mar TI - Enhanced T-cell responses to glioma cells coated with the anti-EGF receptor antibody and targeted to activating FcgammaRs on human dendritic cells. PG - 113-20 LID - 10.1097/CJI.0b013e31815a5892 [doi] AB - The induction of effective immune responses to tumor vaccines requires the preferential activation of effector T cells relative to regulatory or suppressive T cells. Glial tumors commonly overexpress the epidermal growth factor receptor (EGFR), which can be targeted by monoclonal antibodies. Here we show that the coating of glial tumor cells with a clinical grade anti-EGFR antibody, cetuximab, leads to enhanced tumor-specific, interferon-gamma producing CD8+ T cells by dendritic cells (DCs). The selective targeting of monoclonal antibody coated glioma cells to activating Fcgamma receptors (FcgammaRs) on DCs, which is achieved with a blocking antibody to the inhibitory form of FcgammaR, leads to the induction of antitumor immunity without the need for an exogenous maturation stimulus. Importantly, this approach reduces the concurrent induction of regulatory T cells, which can also be depleted to further enhance immunity. These data suggest that immunity to EGFR expressing tumors, including glioma, can be enhanced through the concerted function of antitumor monoclonal antibodies, activating FcgammaR, and DCs. FAU - Banerjee, Devi AU - Banerjee D AD - Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA. FAU - Matthews, Phillip AU - Matthews P FAU - Matayeva, Elyana AU - Matayeva E FAU - Kaufman, Jacob L AU - Kaufman JL FAU - Steinman, Ralph M AU - Steinman RM FAU - Dhodapkar, Kavita M AU - Dhodapkar KM LA - eng GR - AI054375/AI/NIAID NIH HHS/United States GR - M01-RR00102/RR/NCRR NIH HHS/United States GR - P01-AI51573/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunother JT - Journal of immunotherapy (Hagerstown, Md. : 1997) JID - 9706083 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (FCGR2B protein, human) RN - 0 (FOXP3 protein, human) RN - 0 (Forkhead Transcription Factors) RN - 0 (Interleukin-2 Receptor alpha Subunit) RN - 0 (Receptors, IgG) RN - 82115-62-6 (Interferon-gamma) RN - EC 2.7.10.1 (ErbB Receptors) RN - PQX0D8J21J (Cetuximab) SB - IM MH - Antibodies, Monoclonal/immunology/*pharmacology MH - Antibodies, Monoclonal, Humanized MH - Antigen Presentation/drug effects/immunology MH - Antineoplastic Agents/immunology/pharmacology MH - CD8-Positive T-Lymphocytes/*immunology/metabolism MH - Cell Differentiation/immunology MH - Cell Line, Tumor MH - Cetuximab MH - Chemokines/metabolism/pharmacology MH - Coculture Techniques MH - Cytokines/metabolism MH - Dendritic Cells/*drug effects/immunology MH - ErbB Receptors/*immunology/metabolism MH - Forkhead Transcription Factors/analysis MH - Glioma/immunology/metabolism/pathology MH - Humans MH - Interferon-gamma/metabolism MH - Interleukin-2 Receptor alpha Subunit/analysis MH - Lymphocyte Activation/drug effects/immunology MH - Receptors, IgG/*immunology/metabolism MH - T-Lymphocytes, Regulatory/drug effects/immunology/metabolism EDAT- 2008/05/16 09:00 MHDA- 2008/06/13 09:00 CRDT- 2008/05/16 09:00 PHST- 2008/05/16 09:00 [pubmed] PHST- 2008/06/13 09:00 [medline] PHST- 2008/05/16 09:00 [entrez] AID - 00002371-200802000-00001 [pii] AID - 10.1097/CJI.0b013e31815a5892 [doi] PST - ppublish SO - J Immunother. 2008 Feb-Mar;31(2):113-20. doi: 10.1097/CJI.0b013e31815a5892.