Cetuximab ± chemotherapy enhances dendritic cell-mediated phagocytosis of colon cancer cells and ignites a highly efficient colon cancer antigen-specific cytotoxic T-cell response in vitro
Cetuximab is a human/mouse chimeric IgG1 monoclonal antibody (mAb) to epidermal growth factor receptor, approved for colorectal carcinoma treatment in combination with chemotherapy. The immune‐mediated effects elicited by its human fraction of crystallization moiety might critically contribute to th...
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Published in | International journal of cancer Vol. 130; no. 7; pp. 1577 - 1589 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.04.2012
Wiley-Blackwell Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Cetuximab is a human/mouse chimeric IgG1 monoclonal antibody (mAb) to epidermal growth factor receptor, approved for colorectal carcinoma treatment in combination with chemotherapy. The immune‐mediated effects elicited by its human fraction of crystallization moiety might critically contribute to the overall anti‐tumor effectiveness of the antibody. We therefore investigated cetuximab ability to promote colon cancer cell opsonization and phagocytosis by human dendritic cells (DCs) that are subsequently engaged in antigen‐cross presentation to cytotoxic T‐lymphocyte (CTL) precursors. Human colon cancer cell lines were evaluated for susceptibility to DC‐mediated phagocytosis before and after treatment with chemotherapy ± cetuximab in vitro. Human DCs loaded with control or drug‐treated cetuximab‐coated colon cancer cells were used to in vitro generate cytotoxic T cell clones from peripheral blood mononuclear cells of human leucocyte antigen‐A(*)02.01+ donors. T‐cell cultures were characterized for immune‐phenotype and tumor‐antigen specific CTL activity. The results confirmed that treatment of tumor cells with irinotecan + L‐folinate + 5‐flurouracil (ILF) or with gemcitabine + ILF increased tumor antigen expression. Moreover, malignant cells exposed to chemotherapy and cetuximab were highly susceptible to phagocytosis by human DCs and were able to promote their activation. The consequent DC‐mediated cross‐priming of antigens derived from mAb‐covered/drug‐treated cancer cells elicited a robust CTL anti‐tumor response. On the basis of our data, we suggest a possible involvement of CTL‐dependent immunity in cetuximab anti‐cancer effects. |
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Bibliography: | Italian Ministry of Education, University and Research "Programma di Ricerca Scientifica di rilevante interesse Nazionale" (PRIN 2008) ArticleID:IJC26181 ark:/67375/WNG-6B9XF8CB-C istex:2FA1C7FBD5CD52990F2F50D7192CFA29B5AD409E Tel.: +39‐096‐1369‐4324, Fax: +39‐096‐1364‐7341 Tel.: 3905‐7758‐6369, Fax: +3905‐7758‐6133 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0020-7136 1097-0215 |
DOI: | 10.1002/ijc.26181 |