FcγRIIIa polymorphisms and cetuximab induced cytotoxicity in squamous cell carcinoma of the head and neck

Taylor, Rodney J.; Chan, Siaw-Lin; Wood, Aaron; Voskens, Caroline J.; Wolf, Jeffrey S.; Lin, Wei; Chapoval, Andrei I.; Schulze, Dan H.; Tian, Guo‐Liang; Strome, Scott E.

doi:10.1007/s00262-009-0720-9

Cited by 7 publications

(7 citation statements)

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“…EGFR was highly expressed on tumor cells, however, EGFR expression levels were not changed by cetuximab treatment (Figure A). Similarly, FcγRIIIa expression, which plays a pivotal role in cetuximab‐mediated ADCC on NK cells was not changed with or without dexamethasone treatment (Figure B). Next, NK cells (2 × 10 5 /well) from a healthy donor were co‐cultured with tumor cells (2 × 10 4 /well) alone, tumor cells and cetuximab, or tumor cells, cetuximab, and dexamethasone to elucidate whether the steroid affects the ADCC activity of NK cells against tumors.…”

Section: Resultsmentioning

confidence: 88%

Assessment of the change in cetuximab‐induced antibody‐dependent cellular cytotoxicity activity of natural killer cells by steroid

et al. 2015

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Section: Resultsmentioning

confidence: 88%

Assessment of the change in cetuximab‐induced antibody‐dependent cellular cytotoxicity activity of natural killer cells by steroid

et al. 2015

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“…Interestingly, clinical response to cetuximab has been closely correlated with the development of a skin rash, suggesting a systemic effect in only a subset of patients 203. As first shown for rituximab, subsequent studies revealed that HNSCC tumor cell killing in response to cetuximab occurs at least in part through NK cell‐mediated antibody‐dependent cellular cytotoxicity,199, 204, 205 and that the presence of a specific Fc receptor polymorphism can further predict cetuximab cytotoxicity 206. This understanding provides a framework for understanding, at least in part, the mechanism of action of other antibody‐based therapies such as the anti‐EGFR humanized mAb panitumumab and the anti‐VEGF mAb bevacizumab.…”

Section: Discussionmentioning

confidence: 94%

The clinical implications of antitumor immunity in head and neck cancer

et al. 2011

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Recent developments have renewed interest in understanding the interaction between transformed cells and the immune system in the tumor microenvironment. Here, we provide a comprehensive review addressing the basics of tumor immunology in relation to head and neck cancer and the cellular components potentially involved in antitumor immune responses. In addition, we describe the mechanisms by which head and neck cancer cells escape immune-mediated killing and progress to form clinically significant disease. Further, we detail what effects standard anticancer therapies may have on antitumor immune responses and how these responses may be altered by current and investigational immunotherapies. Finally, we discuss future directions that need to be considered in the development of new immunotherapeutics designed to durably alter the immune response in favor of the host.

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“…MDX‐1097 was shown to mediate ADCC, which is considered to be the major mechanism of action elicited by a range of therapeutic antibodies in various haematological malignancies (Cooley et al , ; Hayashi et al , ; Golay et al , ; van Meerten et al , ; Tai et al , ; Taylor et al , ). MDX‐1097‐mediated ADCC activity against MM cells was comparable to other anti‐MM antibodies undergoing development, for example the anti‐CD40 (Hayashi et al , ) and the anti‐CS1 (elotuzumb) (Tai et al , ) mAbs.…”

Section: Discussionmentioning

confidence: 99%

MDX‐1097 induces antibody‐dependent cellular cytotoxicity against kappa multiple myeloma cells and its activity is augmented by lenalidomide

Asvadi¹,

Cuddihy

Dunn³

et al. 2015

Br J Haematol

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SummaryMDX-1097 is an antibody specific for a unique B cell antigen called kappa myeloma antigen (KMA) that consists of cell membrane-associated free kappa light chain (jFLC). KMA was detected on kappa human multiple myeloma cell lines (jHMCLs), on plasma cells (PCs) from kappa multiple myeloma (jMM) patients and on jPC dyscrasia tissue cryosections. In primary jMM samples, KMA was present on CD38+ cells that were CD138 and CD45 positive and/or negative. MDX-1097 exhibited a higher affinity for KMA compared to jFLC and the latter did not abrogate binding to KMA. MDX-1097-mediated antibody-dependent cellular cytotoxicity (ADCC) and in vitro exposure of target cells to the immunomodulatory drug lenalidomide resulted in increased KMA expression and ADCC. Also, in vitro exposure of peripheral blood mononuclear cells (PBMCs) to lenalidomide enhanced MDX-1097-mediated ADCC. PBMCs obtained from myeloma patients after lenalidomide therapy elicited significantly higher levels of MDX-1097-mediated ADCC than cells obtained prior to lenalidomide treatment. These data establish KMA as a relevant cell surface antigen on MM cells that can be targeted by MDX-1097. The ADCC-inducing capacity of MDX-1097 and its potentiation by lenalidomide provide a powerful rationale for clinical evaluation of MDX-1097 alone and in combination with lenalidomide.

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FcγRIIIa polymorphisms and cetuximab induced cytotoxicity in squamous cell carcinoma of the head and neck

Cited by 7 publications

References 0 publications

Assessment of the change in cetuximab‐induced antibody‐dependent cellular cytotoxicity activity of natural killer cells by steroid

Assessment of the change in cetuximab‐induced antibody‐dependent cellular cytotoxicity activity of natural killer cells by steroid

The clinical implications of antitumor immunity in head and neck cancer

MDX‐1097 induces antibody‐dependent cellular cytotoxicity against kappa multiple myeloma cells and its activity is augmented by lenalidomide

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