Tigatuzumab

Chronic moderate-to-severe plaque psoriasis frequently requires long-term biol. treatment, but treatment gaps resulting in relapse are not uncommon.Tildrakizumab is a high-affinity, humanized, IgG1kappa, anti-interleukin-23p19 monoclonal antibody approved to treat plaque psoriasis.This study focus on adult patients with moderate-to-severe plaque psoriasis required tildrakizumab-treated patients who achieved ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75; responders) at Week 28 to be rerandomized to either continued tildrakizumab treatment or withdrawal (placebo) with retreatment with their initial dose of tildrakizumab upon relapse.Of 116 patients continuously treated with tildrakizumab 100 mg after Week 28, 92.6%, 81.5% and 49.6% achieved PASI 50, PASI 75 and PASI 90, resp., at Week 64.From Weeks 28 - 64 of reSURFACE 1, tildrakizumab 100 mg was well tolerated and efficacious in patients receiving continuous treatment; patients withdrawn to placebo recovered response within a median of 28 days.The durability of tildrakizumab responses and rapid regain of efficacy after relapse and retreatment support long-term clin. use of tildrakizumab for the treatment of moderate-to-severe psoriasis.

Methionine addiction is a fundamental and general hallmark of cancer. Gene expression analysis showed that methionine restriction (MR) of methionine-addicted cancer cells increases TNF-related apoptosis-induced ligand receptor-2 (TRAIL-R2) expression. Here, we determined the effects of MR on TRAIL-R2 targeted therapy in pancreatic cancer by the TRAIL-R2 agonist tigatuzumab. Human pancreatic cancer cell lines were cultured in control or methionine-free medium. The effects of MR on TRAIL-R2 expression and sensitivity to tigatuzumab were evaluated in vitro. An orthotopic pancreatic cancer mouse model was established to evaluate the efficacy of MR using oral recombinant methioninase (o-rMETase), and the efficacy of tigatuzumab and their combination. MR enabled tigatuzumab-induced apoptosis, by increasing TRAIL-R2 expression in pancreatic cancer cells in vitro. The protein expression level of the melanoma-associated antigen MAGED2, which reduces TRAIL-R2 expression, was decreased by MR. In the orthotopic pancreatic cancer mouse model, o-rMETase increased TRAIL-R2 expression level in the tumors and enabled the antitumor efficacy of tigatuzumab. MR, effected by o-rMETase, enabled the efficacy of the TRAIL-R2 agonist tigatuzumab by increasing TRAIL-R2 expression in pancreatic cancer. Our results suggest that o-rMETase has clinical potential for treating pancreatic cancer.