RESUMEN
Introduction: Bacillus Calmette-Guerin (BCG) Moreau is under-represented in literature and comparisons with other BCG strains are rare. Material and methods: We conducted a retrospective data analysis in patients with intermediate or high-risk non-muscle invasive bladder cancer (NMIBC) to assess effectiveness and safety of BCG Moreau Polish substrain to BCG RIVM. The primary objective was to describe the real-world effectiveness of BCG Moreau in the treatment of patients with NMIBC in terms of recurrence free survival (RFS) 2 years post-treatment initiation compared to BCG RIVM. Results: The database to be analysed comprised of 967 patients with NMIBC. The primary endpoint was met since BCG Moreau was non-inferior to BCG RIVM in terms of RFS [HR: 0.920 (95%CI: 0.725; 1.168)]. There was no statistically significant difference in all secondary endpoints including time to recurrence, progression-free survival, time to progression, and overall survival. The safety profile of BCG Moreau Polish substrain was consistent with side effects and frequency of complications observed with BCG RIVM and study reports in the literature. Conclusions: BCG Moreau was effective and safe in the treatment of patients with intermediate- or high-risk non-muscle invasive bladder cancer. There was no statistically significant difference in treatment outcome between BCG Moreau and BCG RIVM strains based on real-world data.
RESUMEN
The approval of tyrosine kinase inhibitors and checkpoint inhibitors represented a remarkable progression in the therapeutic landscape for the treatment of metastatic renal cell carcinoma (mRCC). Yet, in the ever-evolving landscape of mRCC treatment, real-world data on these agents, including pazopanib, are scarce. The non-interventional PAZOREAL study investigated the effectiveness and safety of pazopanib (first-line), nivolumab (second-line), and everolimus (second- and third-line) in a real-life setting. The multicentric study included 376 mRCC patients who received first-line treatment with pazopanib and assessed time on the drug (primary endpoint), overall survival, best responses, disease control rates, as well as safety signals and health-related quality of life. The median overall time on the drug was 10.0 months, with first-line pazopanib having a median time on drug of 6.3 months. The median overall survival was 35.9 months. The disease control rate for first-line pazopanib was 56.9%. No new safety signals were detected. PAZOREAL provides valuable real-world data for first-line treatment with pazopanib.
RESUMEN
BACKGROUND: For their application in the area of diagnosis and therapy, single-domain antibodies (sdAbs) offer multiple advantages over conventional antibodies and fragments thereof in terms of size, stability, solubility, immunogenicity, production costs as well as tumor uptake and blood clearance. Thus, sdAbs have been identified as valuable next-generation targeting moieties for molecular imaging and drug delivery in the past years. Since these probes are much less complex than conventional antibody fragments, bacterial expression represents a facile method in order to produce sdAbs in large amounts as soluble and functional proteins. RESULTS: By the combined use of high cell density cultivation media with a genetically engineered E. coli mutant strain designed for the cytoplasmic formation of proper disulfide bonds, we achieved high level of intracellular sdAb production (up to 200 mg/L). Due to a carboxyterminal hexahistidine epitope, the soluble recombinant sdAbs could be purified by one-step immobilized metal affinity chromatography to apparent homogeneity and easily radiolabeled with 99mTc within 1 h. The intradomain disulfide bridge being critical for the stability and functionality of the sdAb molecule was shown to be properly formed in ~96% of the purified proteins. In vitro binding studies confirmed the high affinity and specificity of the expressed sdAb 7C12 towards its molecular target. CONCLUSIONS: Our study demonstrates an efficient cultivation and expression strategy for the production of substantial amounts of soluble and functional sdAbs, which may be adopted for high-yield production of other more complex proteins with multiple disulfides as well.