A5010472756- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Advanced Biosensing Techniques and Applications
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Immune Cell Function and Interaction
- Angiogenesis and VEGF in Cancer
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- HER2/EGFR in Cancer Research
- Biochemical and Structural Characterization
- Galectins and Cancer Biology
- Synthesis and Biological Evaluation
- Renal and related cancers
- Radiopharmaceutical Chemistry and Applications
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- Enzyme function and inhibition
- Lymphatic System and Diseases
- Fibroblast Growth Factor Research
- Cardiac Fibrosis and Remodeling
- Vascular Tumors and Angiosarcomas
- Protein Degradation and Inhibitors
Philochem (Switzerland)
2009-2023
European Institute of Oncology
2014-2021
ETH Zurich
2007-2020
Abstract The alternatively spliced extra‐domain B of fibronectin is one the best characterized markers tumor angiogenesis. Similarly, A (EDA), which can also be inserted in transcript by a mechanism alternative splicing, has been shown to preferentially accumulate around new blood vessels certain tumors, but this antigen not investigated so far as target for antibody‐based biomolecular intervention. We here describe generation 3 human monoclonal antibodies (named F8, B7 and D5), recognize...
Abstract One of the most promising new avenues for development more selective and efficacious cancer therapies relies on antibody-mediated targeted delivery bioactive agents (e.g., cytokines) to tumor environment. The identification quantitative differences in expression accessible vascular proteins metastatic lesions host organs facilitate antibody-based strategies, which should be highly efficient selective, considering fact that an over-exuberant neovasculature is a characteristic feature...
Antibody fragments can recognize their cognate antigen with high affinity and be produced at yields, but generally display rapid blood clearance profiles. For pharmaceutical applications, the serum half-life of antibody is often extended by chemical modification polymers or genetic fusion to albumin albumin-binding polypeptides. Here, we report that site-specific a C-terminal cysteine residue in scFv small organic molecule capable high-affinity binding substantially extends rodents. The...
Elucidating the molecular basis of tumor metastasis is pivotal for eradicating cancer-related mortality. Triple-negative breast cancer (TNBC) encompasses a class aggressive tumors characterized by high rates recurrence and metastasis, as well poor overall survival. Here, we find that promyelocytic leukemia protein PML exerts prometastatic function in TNBC can be targeted arsenic trioxide. We found that, patients, constitutive HIF1A activity induces expression PML, along with number target...
While tumor blood vessels share many characteristics with normal vasculature, they also exhibit morphological and functional aberrancies. For example, the neural adhesion molecule L1, which mediates neurite outgrowth, fasciculation, pathfinding, is expressed on vasculature. Here, using an orthotopic mouse model of pancreatic carcinoma, we evaluated L1 functionality in cancer vessels. Tumor-bearing mice specifically lacking endothelial cells or treated anti-L1 antibodies exhibited decreased...
We describe the cloning and characterization of a novel fusion protein (termed L19‐mIL12), consisting murine interleukin‐12 in single‐chain format, sequentially fused to L19 antibody tandem diabody format. The bound avidly cognate antigen (the alternatively spliced EDB domain fibronectin), retained activity parental cytokine was able selectively localize tumors vivo , as shown by quantitative biodistribution analysis. L19‐mIL12 exhibited potent antitumor immunocompetent mice bearing CT26...
Cancer stem cells (CSC) have been implicated in tumor progression. In ovarian carcinoma (OC), CSC drive formation, dissemination and recurrence, as well drug resistance, thus contributing to the high death-to-incidence ratio of this disease. However, molecular basis such a pathogenic role (OCSC) has elucidated only limited extent. context, functional contribution L1 cell adhesion molecule (L1CAM) OC stemness remains elusive. The expression L1CAM was investigated patient-derived OCSC. genetic...
Several synthetic antibody phage display libraries have been created and used for the isolation of human monoclonal antibodies. The performance libraries, which is usually measured in terms their ability to yield high-affinity binding specificities against target proteins interest, depends both on technical aspects (such as library size quality cloning) design features (which influence percentage functional clones be practical applications). Here, we describe design, construction...
Bcl-xL is an antiapoptotic member of the Bcl-2 protein family and attractive target for development anticancer agents. Here we describe isolation binders to from a DNA-encoded chemical library using affinity-capture selections massively parallel high-throughput sequencing >30,000 sequence tags members. The most potent binder identified, compound 19/93 [(R)-3-(amido indomethacin)-4-(naphthalen-1-yl)butanoic acid], bound with dissociation constant (K(d)) 930 nM was able compete Bak-derived BH3...
Vascular endothelial growth factor C (VEGF-C) is a key mediator of lymphangiogenesis, acting via its receptors VEGF-R2 and VEGF-R3. High expression VEGF-C in tumors correlates with increased lymphatic vessel density, invasion, sentinel lymph node metastasis poor prognosis. Recently, we found that chemically induced skin carcinoma model, drainage from the tumor enhanced lymphangiogenesis facilitated metastatic spread cancer cells lymphatics. Hence, interference VEGF-C/VEGF-R3 axis holds...
Abstract Background The antibody-based targeted delivery of bioactive molecules to tumour vasculature is an attractive avenue concentrate therapeutic agents at cancer sites, while sparing normal organs. L19, F8 and F16 are three fully human monoclonal antibodies, specific splice isoforms fibronectin tenascin-C, which bind sites active tissue remodeling currently in Phase I II clinical trials as radio-immunoconjugates immunocytokines patients with arthritis. In this article, we report the...
Proinflammatory cytokines have been used for several years in patients with advanced cancer but their administration is typically associated severe toxicity hampering application to therapeutically active regimens. This problem can be overcome by using immunocytokines (cytokines fused antibody or fragments) which selectively deliver the cytokine tumor environment. Preclinical and recent clinical results confirmed that this approach a very promising avenue go. We designed an immunocytokine...
Engineered cytokines are gaining importance in cancer therapy, but these products often limited by toxicity, especially at early time points after intravenous administration. 4-1BB is a member of the tumor necrosis factor receptor superfamily, which has been considered as target for therapeutic strategies with agonistic antibodies or using its cognate cytokine ligand, 4-1BBL. Here we describe engineering an antibody fusion protein, termed F8-4-1BBL, that does not exhibit activity solution...
Abstract The use of B cell repertoires for antigen and antibody discovery is on the rise due to emergence new techniques tap into human antigen-experienced repertoire. Recently, many research groups have shown that presence tumor-infiltrating cells or Tertiary Lymphoid Structures (TLS) at tumor sites correlate with improved survival response Immune Checkpoint Inhibitors. Here, we present Kling Biotherapeutic’s platform enables novel therapeutic targets antibody-pairs. We overcome limited...
Abstract IL15 is an immunostimulatory cytokine that holds promises for cancer therapy, but its performance (alone or as partner fusion proteins) has often been limited by suboptimal accumulation in the tumor and very rapid clearance from circulation. Most recently, Sushi Domain (SD, shortest region of receptor α, capable binding to IL15) fused IL15-based anticancer products increase biological activity. Here, we describe two novel antibody proteins (termed F8-F8-IL15 F8-F8-SD-IL15), specific...
Human monoclonal antibodies (mAbs) can routinely be isolated from phage display libraries against virtually any protein available in sufficient purity and quantity, but library design influence epitope coverage on the target antigen. Here we describe construction of a novel synthetic human antibody that incorporates hydrophilic or charged residues at position 52 CDR2 loop variable heavy chain domain, instead serine residue found corresponding germline gene. The was used to isolate mAbs...
Antibody-cytokine fusion proteins (also called 'immunocytokines') represent an emerging class of biopharmaceutical products, which are being considered for cancer immunotherapy. When used as single agents, pro-inflammatory immunocytokines rarely capable inducing complete and durable regression in mouse models patients. However, the combination treatment with conventional chemotherapy or other immune-stimulatory agents typically increases therapeutic efficacy immunocytokines. In this article,...
All Universal Chimeric Antigen Receptor T-cells (UniCAR T-cells) are which have been engineered to recognize a haptenated ligand. Due this feature, UniCAR the potential mediate potent and selective tumor killing only in presence of ligand, thus avoiding long-lasting biocidal effects conventional CAR T-cells. We used fluorescein-labeled versions small organic ligands different antibody formats specific carbonic anhydrase IX (a tumor-associated antigen) order assess whether depended on...
Certain cytokines synergize in activating anti-cancer immunity at the site of disease and it may be desirable to generate biopharmaceutical agents, capable simultaneous delivery cytokine pairs tumor. In this article, we have described cloning, expression characterization IL2-XE114-TNFmut, a dual-cytokine featuring sequential fusion interleukin-2 (IL2) with XE114 antibody scFv format tumor necrosis factor mutant (TNFmut). The protein recognized cognate antigen (carbonic anhydrase IX, marker...