The relevance of ADCC for EGFR targeting: A review of the literature and a clinically-applicable method of assessment in patients

Monteverde, Martino; Milano, Gérard; Strola, Giuliana; Maffi, Monica; Lattanzio, Laura; Vivenza, Daniela; Tonissi, Federica; Merlano, Marco; Nigro, Cristiana Lo

doi:10.1016/j.critrevonc.2015.02.014

Cited by 50 publications

(46 citation statements)

References 26 publications

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“…However, this therapy does not require addiction to the EGFR pathway; instead, it merely requires relatively high surface expression of EGFR in tumor cells as compared to normal cells. The lack of addiction to the EGFR pathway (due to downstream mutations and alternate signaling pathways) and the inability to reproduce ADCC in the absence of an immune system are likely reasons for the relative inefficacy of panitumumab alone in our studies(19–21). We demonstrate successful conjugation of IR700 to panitumumab and the resulting conjugate induces cell death in EGFR-expressing cell lines at low doses of NIR.…”

Section: Discussionmentioning

confidence: 96%

Epidermal Growth Factor Receptor (EGFR)-targeted Photoimmunotherapy (PIT) for the Treatment of EGFR-expressing Bladder Cancer

Railkar

Krane

et al. 2017

Molecular Cancer Therapeutics

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The use of light as a means of therapy for bladder cancer (BC) has a long history but has been hampered by a lack of tumor specificity and therefore, damage to the normal bladder mucosa. Here, we describe a targeted form of photo-therapy called photoimmunotherapy (PIT) which targets EGFR-expressing BC. Anti-EGFR antibody panitumumab (pan) was labeled with the photo-absorber (PA), IRDye 700Dx (IR700), to create a pan IR700 antibody-PA conjugate which is activated by near-infrared radiation (NIR). BC tissue microarray (TMA) and BC cell lines were analyzed for expression of EGFR. Mechanism of PIT induced cell death was studied using proliferation assays, transmission electron microscopy (TEM), and production of reactive oxygen species. Finally, the in vivo effect was studied in xenografts. EGFR staining of TMAs showed that while most BCs have expression of EGFR to a varying degree, squamous cell carcinomas (SCC) have the highest expression of EGFR. Pan IR700 activated by NIR light rapidly killed UMUC-5 cells, a bladder SCC line. Pan alone, pan IR700 without NIR, or NIR alone had no effect on cells. TEM demonstrated that cell death is due to necrosis. Singlet oxygen species contributed towards cell death. NIR-PIT with pan IR700 reduced growth compared to only pan IR700 treated UMUC-5 xenograft tumors. PIT is a new targeted treatment for bladder cancer. Pan IR700-induced PIT selectively kills EGFR-expressing BC cells in vitro and in vivo and therefore warrants further therapeutic studies in orthotopic xenografts of BC and ultimately in patients.

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Section: Discussionmentioning

confidence: 96%

Epidermal Growth Factor Receptor (EGFR)-targeted Photoimmunotherapy (PIT) for the Treatment of EGFR-expressing Bladder Cancer

Railkar

Krane

et al. 2017

Molecular Cancer Therapeutics

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“…Both cetuximab and panitumumab may exhibit more potent activity than that of small-molecule inhibitors in the in vivo setting, which would likely be attributable to antibody-dependent cell-mediated cytotoxicity induced by the mAbs’ triggering of the Fc-RIII receptor on natural killer cells [77]. …”

Section: Egfr-targeted Agentsmentioning

confidence: 99%

Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer

Matsuda

Lim

Wang

et al. 2017

Expert Opinion on Investigational Drugs

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Introduction Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted.

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“…Cetuximab may have the function of mediating antibody-dependent cellular cytotoxicity (ADCC). This monoclonal antibody only achieves dynamic equilibrium after the third week of infusion 48–56. In addition, this biological molecule was approved by the US Food and Drug Administration (FDA) for patients with metastatic colorectal cancer (mCRC), especially for patients who do not tolerate irinotecan (a chemotherapeutic drug), and was also associated with irinotecan for patients who do not tolerate oxaliplatin, irinotecan, and 5-fluorouracil (5-FU) 57,58…”

Section: Supporting Treatment With Monoclonal Antibodiesmentioning

confidence: 99%

“…When compared with cetuximab, it is a murine antibody with reduced portions. However, panitumumab is not able to mediate ADCC 56,63. The mechanism of action of panitumumab is due to its binding to EGFR and blocking of this receptor.…”

Section: Supporting Treatment With Monoclonal Antibodiesmentioning

confidence: 99%

Immunotherapy for the treatment of colorectal tumors: focus on approved and in-clinical-trial monoclonal antibodies

Françoso¹,

Simioni²

2017

DDDT

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Colorectal cancer is considered a disease of the elderly population. Since the number of geriatric patients continues to rise, monoclonal antibody therapy is the most promising therapy in the recent research. Presently, the monoclonal antibodies most frequently used in the treatment of colorectal tumors are bevacizumab, cetuximab, panitumumab, and ramucirumab. Bevacizumab is a monoclonal antibody that acts on VEGF. Cetuximab and panitumumab act on EGFR. Ramucirumab binds directly to the ligand-binding pocket of VEGFR-2 to block the binding of VEGF-A, VEGF-C, and VEGF-D. These monoclonal antibodies, alone or in association with radiotherapy or chemotherapy, are presenting good results and are increasing patient survival, despite the side effects. Due to the limited number of molecules available, several studies are trying to develop new monoclonal antibodies for the treatment of colorectal tumors. Among those being studied, some recent molecules are in phase I and/or II trials and are yielding advantageous results, such as anti-DR5, anti-Fn14, anti-IGF-1R, anti-EGFR, anti-NRP1, and anti-A33 antibodies. This has been successful in reducing side effects and in treating nonresponsive patients.

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The relevance of ADCC for EGFR targeting: A review of the literature and a clinically-applicable method of assessment in patients

Cited by 50 publications

References 26 publications

Epidermal Growth Factor Receptor (EGFR)-targeted Photoimmunotherapy (PIT) for the Treatment of EGFR-expressing Bladder Cancer

Epidermal Growth Factor Receptor (EGFR)-targeted Photoimmunotherapy (PIT) for the Treatment of EGFR-expressing Bladder Cancer

Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer

Immunotherapy for the treatment of colorectal tumors: focus on approved and in-clinical-trial monoclonal antibodies

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