Muromonab-CD3 solution for injection 5mg/5ml ampoules

Studies have shown that patients who undergo heart transplantation (HTx) are at an increased risk for developing skin cancer. This condition can add physiological and psychological burden to patients. Therefore, assessing the incidence and identifying risk factors for skin cancer are crucial steps in its prevention. The purpose of this skin study is to systematically evaluate the incidence and risk factors of skin cancer in HTx. Two researchers independently conducted literature searches across 8 databases. The search covered publications from the establishment of the database through October 1, 2024. After screening title, abstract, and the full text, 34 eligible cohort studies were included. The studies were evaluated using the New castle-Ottawa Scale (NOS) for non-randomized studies, and papers selection followed PRISMA guidelines. The meta-analysis was conducted using the Stata 15.0 software. Among 34 cohort studies on HTx, the pooled incidence of skin cancer was 16% (95% CI: 14-19%). The incidences by type were 10% (95% CI: 8-12%) for squamous cell carcinoma and 8% (95% CI: 6-9%) for basal cell carcinoma. Regionally, the highest incidence was observed in the USA 22% (95% CI: 18-27%). Risk factors significantly associated with skin cancer included age (RR: 1.08, 95% CI: 1.04-1.11), male (RR: 1.53, 95% CI:1.11-2.12), white race (RR: 10.23, 95% CI: 7.32-14.30), smoking history (RR:1.26, 95% CI:1.05-1.51), prolonged sunlight exposure (≥ 2500 h) (RR:3.66, 95% CI: 2.11-6.36), pre-transplant cancer (RR: 1.61, 95% CI: 1.43-1.82), muromonab-CD3 (OKT3) (RR: 2.61, 95% CI: 2.11-3.24). The higher incidence of skin cancer observed in this study highlights the urgent need for follow-up care in heart transplant recipients. To address this, tailored skin cancer prevention strategies should be implemented, focusing on modifiable risk factors. Our findings provide a theoretical foundation to help healthcare professionals prevent and manage skin cancer in heart transplant patients.Patient or Public Contribution: YY, and HPY, were responsible for the conception and design of the study. YYS, FYL, and HPY, were responsible for the acquisition, analysis and interpretation of the data. All of the authors drafted the article or revised it critically for important intellectual content and provided final approval of the version to be submitted.

Abstract licence: CC BY-NC-ND

Antibody-based cancer therapies have been evolving at a rapid pace in the pharmaceutical market. Bispecific antibody-drug conjugates that engage immune cells to target and kill cancer cells with precision have inspired the development of immunotherapy. Miniaturized antibody fragments such as diabodies, nanobodies, or single-chain variable fragments (scFvs) hold great promise as antibody-drug conjugates as they specifically target tumor tissue and can penetrate it. Here, we optimized the soluble periplasmic expression of the scFv OKT3 comprising the variable VH and VL domains of the mouse anti-human CD3 antibody muromonab-CD3 (trade name Orthoclone OKT3) in E. coli. By an expansion of the genetic code, we site-specifically incorporated the reactive non-canonical amino acid Nε-((2-azidoethoxy)carbonyl)-L-lysine (AzK) into scFv OKT3 using an orthogonal pyrrolysyl-tRNA synthetase/tRNACUA pair. To confirm the AzK incorporation and to demonstrate the accessibility of the reactive azide group, we conjugated a fluorophore to scFv OKT3 AzK variants by copper-free strain-promoted alkyne-azide cycloaddition (‘click chemistry’). The scFv OKT3 wild type and the AzK variants bound T cells at nanomolar concentrations. In this study, a ‘ready-to-click’ scFv OKT3 was successfully developed for future applications, e.g. as controlled anti-T cell antibody-drug conjugate or bispecific T cell engager and for imaging immune T cell migration in cancers.

Abstract licence: CC BY

OBJECTIVE: Systemic lupus erythematosus (SLE) patients are at risk during the COVID-19 pandemic, yet the underlying molecular mechanisms remain incompletely understood. This study sought to analyze the potential molecular connections between COVID-19 and SLE, employing a bioinformatics approach to identify effective drugs for both conditions. METHODS: The data sets GSE100163 and GSE183071 were utilized to determine share differentially expressed genes (DEGs). These DEGs were later analyzed by various bioinformatic methods, including functional enrichment, protein-protein interaction (PPI) network analysis, regulatory network construction, and gene-drug interaction construction. RESULTS: A total of 50 common DEGs were found between COVID-19 and SLE. Gene ontology (GO) functional annotation revealed that "immune response," "innate immune response," "plasma membrane," and "protein binding" were most enriched in. Additionally, the pathways that were enriched include "Th1 and Th2 cell differentiation." The study identified 48 genes/nodes enriched with 292 edges in the PPI network, of which the top 10 hub genes were CD4, IL7R, CD3E, CD5, CD247, KLRB1, CD40LG, CD7, CR2, and GZMK. Furthermore, the study found 48 transcription factors and 8 microRNAs regulating these hub genes. Finally, four drugs namely ibalizumab (targeted to CD4), blinatumomab (targeted to CD3E), muromonab-CD3 (targeted to CD3E), and catumaxomab (targeted to CD3E) were found in gene-drug interaction. CONCLUSION: Four possible drugs that targeted two specific genes, which may be beneficial for COVID-19 patients with SLE.

Abstract licence: CC BY

Introduction A diverse range of innovative biological therapies is being developed to treat various human diseases. The safety assessment of these biologics is a critical factor determining clinical success. Enhanced humanised mouse models have the potential to revolutionise immunotoxicological profiling by refining procedures for effective in vivo safety assessments. Methods We evaluated a novel reference panel of recombinant monoclonal antibodies (mAbs), 19/156, with varying cytokine release (CR) potential to assess the sensitivity of specific humanised mouse models. The in vitro CR capacity of the reference panel has previously been evaluated in an international collaborative study. We present here the in vivo assessment of the reference Ab panel using NOD-scid-gamma (NSG) mice reconstituted with either umbilical cord-derived hematopoietic human (CD34 + ) stem cells (HSC) or human peripheral blood mononuclear cells (PBMC) from healthy donors. Results Our manuscript discusses a comparative evaluation of both forms of engraftment and the CR patterns in response to the reference panel. The in vivo CR pattern is discussed in relation to in vitro assays using the same PBMC donor cohort. The manuscript discusses the utility of these humanised mice as a model for translational use in hazard identification and preclinical safety assessment. Discussion The results highlight the importance of incorporating standardised reference materials to evaluate, qualify, and harmonise preclinical models for translational use. This approach aims to enhance the predictability and reliability of both in vitro and in vivo safety assessments, thereby supporting the development of safe and effective biological therapies.

Abstract licence: CC BY