Chronic urticaria was frequently associated with thyroid autoimmunity. We did not observe significant relationship between chronic autoimmune urticaria and thyroid autoimmunity and we suggest these are tangential, parallel autoimmune events.”
“Antibodies can undergo a variety of covalent and non-covalent degradation reactions that have adverse effects
on efficacy, safety, manufacture and storage. We had identified an antibody to Angiopoietin 2 (Ang2 mAb) that neutralizes Ang2 binding to its receptor in vitro and inhibits tumor growth in vivo. Despite favorable pharmacological activity, the Ang2 mAb DMXAA preparations were heterogeneous, aggregated rapidly and were poorly expressed. Here, we report the engineering
of the antibody variable and constant domains to generate an antibody with reduced propensity to aggregate, enhanced homogeneity, 11 degrees C elevated T-m, 26-fold improved level of expression and retained activity. The engineered molecule, MEDI-3617, is now compatible with the large scale material supply required for clinical trials and is currently 4SC-202 inhibitor being evaluated in Phase 1 in cancer patients. This is the first report to describe the stability engineering of a therapeutic antibody addressing non canonical cysteine residues and the design strategy reported here is generally applicable to other therapeutic antibodies and proteins.”
“Background and objective: We conducted a systematic
review of prospective, randomized, controlled trials (RCT) to examine whether histology had a treatment modifying effect (TME) on the efficacy outcomes of chemotherapeutic agents in patients with advanced (stage IIIB-IV) non-small cell lung cancer (NSCLC).
Methods: Potentially pertinent publications were reviewed in full to determine if there was any TME by histology for overall survival (OS), progression-free survival (PFS) or treatment selleck kinase inhibitor response rate (TRR).
Results: Data from three pemetrexed RCT, comparing (i) pemetrexed versus docetaxel, (ii) pemetrexed and cisplatin versus gemcitabine and cisplatin, and (iii) pemetrexed versus placebo, showed a statistically significant TME by histology for OS and PFS. One trial comparing pemetrexed and carboplatin versus gemcitabine and carboplatin found no significant associations between histology and OS. The results of this systematic review indicate that pemetrexed appears to have the most consistent treatment-by-histology interaction effect on the efficacy outcomes of chemotherapeutic agents in patients with advanced or metastatic NSCLC. Patients with non-squamous histology gain the greatest benefit from treatment with pemetrexed. Conversely, patients with squamous cell disease appeared to experience poorer OS when pemetrexed was compared with other active treatments, and similar OS when compared with placebo.