Enhanced T-cell responses to glioma cells coated with the anti-EGF receptor antibody and targeted to activating FcgammaRs on human dendritic cells.
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.
Banerjee
Devi
D
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA.
Matthews
Phillip
P
Matayeva
Elyana
E
Kaufman
Jacob L
JL
Steinman
Ralph M
RM
Dhodapkar
Kavita M
KM
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D000068818:Cetuximab; D018925:Chemokines / Q000378:metabolism / Q000494:pharmacology; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000032:analysis; D005910:Glioma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018925:Chemokines; D016207:Cytokines; C499173:FCGR2B protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D017452:Receptors, IgG; D007371:Interferon-gamma; D066246:ErbB Receptors; D000068818:Cetuximab