ABT-414 is an anti-EGFR (epidermal growth factor receptor) monoclonal antibody drug conjugate (ADC). As an ADC, ABT-414 is designed to be stable in the bloodstream and only release the potent cytotoxic agent once inside targeted cancer cells. Developed by AbbVie researchers with components in-licensed from Life Science Pharmaceuticals, ABT-414 is currently being investigated for the treatment of glioblastoma multiforme, the most common and most aggressive malignant primary brain tumor. ABT-414 is also in clinical trials for the treatment of patients with squamous cell tumors. ABT-414 is an investigational compound and its efficacy and safety have not been established by the FDA.
About Glioblastoma Multiforme
Glioblastoma is the most common and most aggressive type of malignant primary brain tumor. Each year in the U.S. and Europe, two to three out of every 100,000 people are diagnosed with glioblastoma, which has a five year survival rate of less than 3 percent. Prior to diagnosis, most patients experience a serious symptom of glioblastoma, such as a seizure. Typically patients succumb to the disease approximately 15 months after diagnosis. Treatment for glioblastoma remains challenging and no long-term treatments are currently available. Standard treatment is surgical resection, radiotherapy and concomitant adjunctive chemotherapy. More than 8,700 patients are enrolled in industry-sponsored clinical studies.
Monoclonal antibody 806 targets a proprietary epitope on the Epidermal Growth Factor Receptor (EGFR). A differentiating feature of 806 is that it binds to cancer cells, but not to cells of normal tissue. The unique specificity of mAb806 offers an advantage over current EGFR ligand blocking antibodies which all bind to normal liver, skin and gut in humans. Epitope mapping studies have confirmed that mAb806 binds to a unique epitope on the EGFR which is exposed in the transitional untethered form of the receptor. MAb806 therefore represents a novel approach to tumor specific targeting of cancer cells.
Preclinical studies with mAb806 have shown that it specifically targets cell lines overexpressing wt and delta2-7EGFR, causes dramatic reduction in tumor growth when given alone, combined with other biologics and radiotherapy. MAb806 has been shown to be superior to other anti-EGFR antibodies and tyrosine kinase inhibitors in treating tumors with delta2-7EGFR mutations or EGFR kinase domain mutations in-vivo. A Phase I first-in-man clinical trial of human IgG1 chimeric mAb806 was completed to identify the safety, biodistribution and targeting of ch806 to tumor in cancer patients. This trial confirmed the tumor specificity of ch806, and lack of normal tissue uptake or toxicity in cancer patients.
MAb806 also has potential for delivery of payloads to cancer cells, due to its internalization properties in tumors and lack of normal cell binding. Life Science Pharmaceuticals (LSP) has also demonstrated that EGFR is activated in psoriasis and the unique epitope of 806 is expressed in immunohistochemistry studies of psoriatic tissues. Antibody 806 was generated and characterized by scientists in the Ludwig Institute for Cancer Research, and is exclusively licensed to LSP world-wide. As a result of this license and internally developed patents, Life Science Pharmaceuticals controls a robust patent portfolio for the mAb806 program.
LSP has licensed mAb806 to Abbott Biotechnology, and is supporting further pre-clinical and clinical development of humanized 806 in multiple cancer indications, including lung, colon, head and neck cancer, and brain tumors.
Information about clinical sites and contact information can be accessed here.
References: Luwor et al, Cancer Res 15: 5355-5361, 2001; Jungbluth et al, PNAS 100 (2): 639-644, 2003; Johns et al, J Biol Chem 279(29):30375-84, 2004; Panousis et al, Br J Cancer 92(6): 1069-77, 2005; Perera et al, Neoplasia 9(12): 1099-1110, 2007; Johns et al, Clin Cancer Res 13(6): 1911-1925, 2007; Scott et al, PNAS 104: 4071-4076, 2007; Garrett et al, PNAS 106(13): 5082-7, 2009.
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