Development of a complete human anti‐human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer

Abstract

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. Up to 20% of oral dysplasia cases have been suggested to undergo malignant transformation to OSCC; however, there are no methods to predict OSCC development. In this study, to identify the genes associated with oral dysplasia progression, we performed genomic copy number analyses of genomic DNA samples isolated from primary oral dysplasia and OSCC via the microdissection method and found elevated expression of transferrin receptor C (TfR1/TFRC) with genomic amplification in oral dysplasia and OSCC. The expression rate of TFRC in OSCC was significantly higher than that in dysplasia, suggesting that OSCC disease progression might be related to TFRC expression. Additionally, we investigated the in vitro and in vivo impacts of a newly established anti-human TFRC monoclonal antibody, which was isolated from a human cDNA library using the phage-display method, on cell proliferation and survival. The anti-TFRC antibody blocked the interaction between transferrin and TFRC and consequently inhibited iron uptake, leading to the iron deprivation-mediated suppression of cell growth and induction of apoptosis. Moreover, we demonstrated that the anti-TFRC antibody efficiently inhibited tumor growth in a murine xenograft OSCC model. Therefore, we suggest our developed complete human anti-human TFRC antibody as a useful, novel treatment for oral dysplasia and OSCC.

Insights into the effector functions of human IgG3 in the context of an antibody targeting transferrin receptor 1

“…In addition, the baculovirus-expressed version of this chimeric antibody, chi7579 mAb, induced ADCC and CDC against human hepatocellular carcinoma cells HepG2 and breast adenocarcinoma cells MCF-7 in the presence of human PBMC and rabbit complement, respectively (Shen et al, 2009). Furthermore, anti-TFRC, a human IgG against human TfR1, mediated ADCC against human oral squamous cell carcinoma cells in the presence of human PBMC (Nagai et al, 2014). This antibody also exhibited anti-tumor effects against these malignant cells in a xenograft mouse model (Nagai et al, 2014).…”

“…Furthermore, anti-TFRC, a human IgG against human TfR1, mediated ADCC against human oral squamous cell carcinoma cells in the presence of human PBMC (Nagai et al, 2014). This antibody also exhibited anti-tumor effects against these malignant cells in a xenograft mouse model (Nagai et al, 2014). The above results, together with ours, suggest that ADCC and/or CDC may play a role in the protection elicited by antibodies targeting TfR1 in vivo .…”

Secretory IgA accumulated in the airspaces of idiopathic pulmonary fibrosis and promoted VEGF, TGF-β and IL-8 production by A549 cells

“…a). In general, compared to slowly proliferating cells, highly proliferating cells express high levels of TfR/CD71 to meet their iron demands, and this was also the case with A549 cells . Hyperplastic epithelial cells in IPF lungs also expressed a high level of TfR/CD71 (Fig.…”

Blocking transferrin receptor inhibits the growth of lung adenocarcinoma cells in vitro

“…Transferrin receptor plays a crucial role in the cellular uptake of iron, and cellular iron deficiency arrests cell growth, leading to cell death . TfR is expressed more abundantly in malignant tissues than in normal tissues because cancer cells require copious amounts of iron to maintain their high proliferation rates . Therefore, TfR is an attractive target for immunotherapy and for the delivery of cytotoxic agents because of its increased expression in malignant compared to normal cells .…”