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protein and negatively regulated canonical TGF-β signalling. This could inhibit
EMT activation by the ligand. So the obvious means of approach to the inhibition
of TGF-β signalling are monoclonal antibodies raised TGF-β family receptors, tar-
geting Smad and related signalling components and using antisense RNAs to inhibit
TGE-β ligands and their receptors at the mRNA level, which was proposed many
years ago.
Antisense Oligonucleotide Trabedersen (AP 12009)
Trabedersen (AP 12009) is an antisense oligonucleotide inhibitor which targets TGF-
β2 mRNA. Many studies have been reported on the effectiveness of Trabedersen on
several forms of cancer. A randomized controlled international phase III clinical trial
of recurrent or refractory anaplastic astrocytoma and glioblastoma began in early
2009, wherein Trabedersen is administered by convection-enhanced delivery (CED),
an intratumoral drug delivery method, which is highly effective in patients with
malignant brain tumours.
Schlingensiepen et  al. (2011) studied the antitumour activity of Trabedersen
in pancreatic cancer cells and in vivo xenograft of metastatic pancreatic cancer in
muirine hosts. In vitro Trabedersen at μM concentration effectively reduced TGF-
β2 secretion by pancreatic cell lines and inhibited cell proliferation, and migration
of pancreatic cancer cells. In vivo xenografts of metastatic pancreatic cancer treated
intraperitoneally significantly inhibited tumour growth, lymph node metastasis and
angiogenesis (Schlingensiepen et  al., 2011). A phase I clinical trial is under way
in advanced pancreatic carcinoma, metastatic melanoma and metastatic colorec-
tal carcinoma. Trabedersen is administered intravenously to patients with advanced
tumours over producing TGF-β2 (NCT00844064).
Anti-TGF- β Monoclonal Antibodies
Lerdelimumab, Metelimumab and Fresolimumab
Two monoclonal antibodies against TGF-β have received some attention.
Lerdelimumab (CAT-152) might be useful in treating some ophthalmological con-
ditions. It reduces TGF-β fibrotic effects in Graves' ophthalmopathy (Pohlers et al.,
2009). It was shown some time ago to be able to inhibit TGF-β induced effects and
suppress posterior capsule opacification, which occurs after extracapsular cataract
surgery and intraocular lens implantation (Wormstone et  al., 2002). Lerdelimumab
prevents, not invariably, corneal scarring after trabeculectomy. Metelimumab (CAT-
192) is a human monoclonal TGF-β1 antibody which is being touted as potential
treatment of diffuse cutaneous systemic sclerosis (Sorbera, 2004). The human anti-
TGF-β antibody Fresolimumab is said to neutralise all isoforms of TGF-β and has
immunomodulatory ability. It has been the subject of phase I trial in patients with
refractory primary focal segmental glomerulosclerosis (FSGS) to assess the safety
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