A5049333472- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Chemotherapy-induced cardiotoxicity and mitigation
- Cancer, Stress, Anesthesia, and Immune Response
- Radiopharmaceutical Chemistry and Applications
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- HER2/EGFR in Cancer Research
- Galectins and Cancer Biology
- Virus-based gene therapy research
- Nanoplatforms for cancer theranostics
- SARS-CoV-2 and COVID-19 Research
- Glycosylation and Glycoproteins Research
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Platelet Disorders and Treatments
- Macrophage Migration Inhibitory Factor
- Cancer Research and Treatments
- Pharmacological Receptor Mechanisms and Effects
- Brain Metastases and Treatment
- Heparin-Induced Thrombocytopenia and Thrombosis
- SARS-CoV-2 detection and testing
University of Naples Federico II
2017-2025
Ceinge Biotecnologie Avanzate (Italy)
2017-2025
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
2021-2024
Federico II University Hospital
2017-2022
Institute for Experimental Endocrinology and Oncology
2020
Sechenov University
2020
Institute of Biostructure and Bioimaging
2020
Fondazione IRCCS Istituto Nazionale dei Tumori
2020
Abstract One of the most promising cancer immunotherapies is based on bi-specific T-cell engagers (BiTEs) that simultaneously bind with one arm to a tumor-associated antigen tumor cells and other CD3 complex T form TCR-MHC independent immune synapse. We previously generated four novel tri-specific tribodies made up Fab targeting 5T4, an oncofetal expressed several types tumors, scFv cells, additional specific for checkpoint (IC), such as PD-1, PD-L1 or LAG-3. To verify their advantages over...
Several strategies based on immune checkpoint inhibitors (ICIs) have been developed for cancer therapy, opening to advantages in outcomes. However, several ICI-induced side effects emerged these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality. We studied the cytotoxic and pro-inflammatory properties Ipilimumab Nivolumab, underlying pathways cytokine storm involved.Co-cultures human cardiomyocytes lymphocytes were exposed or Nivolumab; cell...
Abstract Background Triple-negative breast cancer (TNBC) is a uniquely aggressive with high rates of relapse due to resistance chemotherapy. TNBC expresses higher levels programmed cell death-ligand 1 (PD-L1) compared other cancers, providing the rationale for recently approved immunotherapy anti-PD-L1 monoclonal antibodies (mAbs). A huge effort dedicated identify actionable biomarkers allowing combination therapies immune-checkpoint blockade. Platelet-derived growth factor receptor β...
Immune checkpoint inhibitors (ICIs) have significantly changed the oncology clinic in recent years, improving survival expectations cancer patients. ICI therapy a broad spectrum of side effects from endocrinopathies to cardiovascular diseases. In this study, pro-inflammatory and pro-fibrotic short-term ICIs preclinical models were analyzed.Firstly, human vitro model, cardiomyocytes co-cultured with hPBMC exposed (with CTLA-4 or PD-1 blocking agents, at 200 nM) for 72 h. After treatment,...
Abstract The novel antibody-based immunotherapy in oncology exploits the activation of immune system mediated by immunomodulatory antibodies specific for checkpoints. Among them, programmed death ligand-1 (PD-L1) is particular interest as it expressed not only on T-cells, but also other cells and a large variety cancer cells, such breast considering its high expression both ErbB2-positive Triple Negative Breast Cancers. We demonstrate here that PD-L1_1, anti-PD-L1 T -cell stimulating...
Monoclonal antibodies have been approved by the Food and Drug Administration for treatment of various human cancers. More recently, oligonucleotide aptamers risen increasing attention cancer therapy thanks to their low size (efficient tumor penetration) lack immunogenicity, even though short half-life effector functions still hinder clinical applications. Here, we demonstrate, first time, that two novel bispecific conjugates, consisting an anti-epidermal growth factor receptor (EGFR) aptamer...
Long-chain polyphosphates inhibit SARS-CoV-2 infection by targeting a host receptor and viral RNA polymerase.
Gut microbiota plays a key role in modulating responses to cancer immunotherapy melanoma patients. Oncolytic viruses (OVs) represent emerging tools therapy, inducing potent immunogenic cell death (ICD) and recruiting immune cells tumors, poorly infiltrated by T cells. We investigated whether the antitumoral activity of oncolytic adenovirus Ad5D24-CpG (Ad-CpG) was gut microbiota-mediated syngeneic mouse model observed that ICD weakened vancomycin-mediated perturbation microbiota. Ad-CpG...
Background Immune checkpoint blockade in monotherapy or combinatorial regimens with chemotherapy radiotherapy have become an integral part of oncology recent years. Monoclonal antibodies against CTLA-4 PD-1 PDL-1 are the most studied ICIs randomized clinical trials, however, more recently, anti-LAG3 (Lymphocyte activation gene-3) antibody, Relatlimab, has been approved by FDA combination Nivolumab for metastatic melanoma therapy. Moreover, Atezolizumab is actually under study association...
Immune checkpoints are emerging as novel targets for cancer therapy, and antibodies against them have shown remarkable clinical efficacy with potential combination treatments to achieve high therapeutic index. This work aims at providing a approach the generation of several human immunomodulatory capable binding their in native conformation useful applications.We performed massive parallel screening phage libraries by using first time activated lymphocytes generate large collections...
The immune checkpoint CTLA-4 (cytotoxic T-lymphocyte-antigen 4), which inhibits the co-stimulatory CD28 signal on T cells, has been recently found expressed other cell populations, such as tumor and natural killer (NK) cells. We tested for first time effects of ipilimumab, human anti-CTLA4 mAb in clinical use, these cells that it growth expressing also absence lymphocytes, efficiently activates NK thus suggesting an important unexplored role ipilimumab-modulated responses. Interestingly,...
Cardiovascular diseases, including thrombosis, are the leading cause of mortality worldwide. The generation monoclonal antibodies (mAb) targeting specific coagulation factors could provide more targeted and safer anticoagulant therapies. Factor V (FV) is a critical cofactor in prothrombinase complex, which catalyzes conversion prothrombin to thrombin, key enzyme cascade. We isolated novel human antibody FV by using phage display technology. selection occurred panning large repertoire phages...
Use of monoclonal antibodies is emerging as a highly promising and fast-developing scenario for innovative treatment viral, autoimmune tumour diseases. The search diagnostic therapeutic currently depends on in vitro screening approaches, such phage yeast display technologies. Antibody production still represents critical step preclinical clinical evaluations. Accordingly, improving an opportunity, to facilitate downstream target validations. SINEUP RNAs are long non-coding transcripts,...
The rare but dangerous adverse events evidenced after massive vaccination against SARS-CoV-2 are represented by thrombosis and thrombocytopenia. patients diagnosed with severe COVID-19 may develop a pro-thrombotic state much higher frequency, thus we decided to investigate the role of Spike protein (the only common product two conditions) or anti-Spike antibodies in etiopathogenesis thrombosis. A pathogenic Platelet Factor 4 (PF4)-dependent syndrome, unrelated use heparin therapy, has been...
Oncolytic virotherapy is an emerging therapeutic approach based on replication-competent viruses able to selectively infect and destroy cancer cells, inducing the release of tumor-associated antigens thereby recruiting immune cells with a subsequent increase in antitumoral response. To anticancer activity, we engineered specific oncolytic adenovirus expressing single-chain variable fragment antibody against PD-L1 combine blockage PD-1/PD-L1 interaction activity Onc.Ad5. assess its efficacy,...
Among the therapies against pandemic SARS-CoV-2 virus, monoclonal Antibodies (mAbs) targeting Spike glycoprotein represent good candidates to interfere in Spike/ACE2 interaction, preventing virus cell entry. Since anti-spike mAbs, used individually, might be unable block entry case of resistant mutations, we designed an innovative strategy for isolation multiple novel human scFvs specific binding domain (RBD) Spike. By panning a large phage display antibody library on immobilized RBD,...
The cytotoxic T lymphocyte-antigen 4 (CTLA-4) has been considered an IC exclusively expressed on cells, where it counteracts the co-stimulatory CD28 receptor, by competing for its binding to CD-80 and CD-86. We recently found that is also tumor NK suggesting other possible unknown roles of CTLA-4. To shed light these novel aspects CTLA-4, we used Ipilimumab, first FDA approved human antibody targeting in parallel studies with two mAbs isolated using efficient phage display selection strategy...
Abstract Background Immunotherapy based on Bi-specific T Cell Engagers (TCE) represents one of the most attractive strategy to treat cancers resistant conventional therapies. TCE are antibody-like proteins that simultaneously bind with arm a Tumor Associated Antigen (TAA) cancer cells and other CD3 complex T-cell form TCR-independent immune synapse circumvent Human Leucocyte restriction. Among them, tribodies, such as Tb535H, bi-specific molecule, made up Fab scFv domain both targeting 5T4...
Antibodies targeting Immune Checkpoints (IC) on tumor infiltrating lymphocytes improve immune responses against cancer. Recently, the expression of some ICs has also been reported cancer cells. We used clinically validated Ipilimumab and Nivolumab other novel human antibodies Cytotoxic T- lymphocyte-antigen 4 (CTLA-4), Programmed Death receptor-1 (PD-1) Ligand 1 (PD-L1) to shed light functions these in show here for first time that all antagonistic mAbs are able reduce Erk phosphorylation...
Cancer immunotherapy has already shown significant improvements by combining different antibodies specific for distinct immune checkpoints, such as Ipilimumab and Nivolumab. Here, we tested combinatorial treatments of immunomodulatory antibodies, previously generated in our laboratory, their effects on hPBMC activation, either upon stimulation with SEB or co-cultures tumor cells cytokine secretion assays. We found that some them showed additive synergistic effects, the basis these...
The recent pandemic years have prompted the scientific community to increasingly search for and adopt new more efficient therapeutic diagnostic approaches deal with a infection. In addition development of vaccines, which has played leading role in fighting pandemic, monoclonal antibodies also represented valid approach prevention treatment many cases CoronaVirus Disease 2019 (COVID-19). Recently, we reported human antibody, named D3, showing neutralizing activity against different SARS-CoV-2...
The Tyrosine Kinase Receptor ErbB2 (HER2) when overexpressed in breast cancer (BC) is associated with poor prognosis. monoclonal antibody Trastuzumab has become a standard treatment of ErbB2+BC. limited efficacy, often meets resistance and induces cardiotoxicity. T-cell recruiting bispecific derivatives (TRBA) offer more effective alternative to therapy. We evaluated panel TRBAs targeting 3 different epitopes on the receptor either bivalent tribody structure or as monovalent scFv-fusion...
The affinity engineering is a key step to increase the efficacy of therapeutic monoclonal antibodies and yeast surface display most widely used powerful maturation approach, achieving picomolar binding affinities. In this study, we provide an optimization methodology, applied generation potentially high targeting immune checkpoint PD-L1. coupled 10-cycle error-prone mutagenesis heavy chain complementarity determining region 3 anti‐PD-L1 scFv, previously identified by phage display, with...