381 research outputs found
Novel Strategies to Improve Rituximab Efficacy in Non-Hodgkin's Lymphomas
No full textNon-Hodgkin’s lymphomas (NHLs) are the second fastest growing cancer in terms of incidence and deaths in the United States and Europe. NHLs are a heterogeneous cancer group including several haematological neoplasias with different degree of aggressiveness. In spite of the progresses, conventional therapies do not ensure long-term survival [1]. The NHL patients, who have a poor life expectation, could take advantage from innovative therapeutic strategies, such as immunotherapy. Specific antibodies can preferentially bind tumour cells over normal tissues. This specificity is based upon characteristics (surface antigens) that are completely independent from the parameters that allow for differential toxicity of chemo- and radiotherapy. The vascular nature of most lymphomas and their antigen expression make these tumours a favourable setting for treatment with monoclonal antibodies. In fact, the first successful use of antibodies as treatments for cancer was demonstrated in NHLs [2,3]. CD20 has been largely exploited as target antigen for immunotherapy with antibodies because it is expressed at high levels on B-lymphoma cells and is not expressed on stem cells [4].</p
Plant Toxin-Based Immunotoxins for Cancer Therapy: A Short Overview
No full textImmunotoxins are chimeric proteins obtained by linking a toxin to either an intact antibody or an antibody fragment. Conjugation can be obtained by chemical or genetic engineering, where the latter yields recombinant conjugates. An essential requirement is that the target molecule recognized by the antibody is confined to the cell population to be deleted, or at least that it is not present on stem cells or other cell types essential for the organism’s survival. Hundreds of different studies have demonstrated the potential for applying immunotoxins to many models in pre-clinical studies and in clinical trials. Immunotoxins can be theoretically used to eliminate any unwanted cell responsible for a pathological condition. The best results have been obtained in cancer therapy, especially in hematological malignancies. Among plant toxins, the most frequently employed to generate immunotoxins are ribosome-inactivating proteins, the most common being ricin. This review summarizes the various approaches and results obtained in the last four decades by researchers in the field of plant toxin-based immunotoxins for cancer therapy
Bouganin, an attractive weapon for immunotoxins
No full textBougainvillea (Bougainvillea spectabilis Willd.) is a plant widely used in folk medicine and many extracts from different tissues of this plant have been employed against several pathologies. The observation that leaf extracts of Bougainvillea possess antiviral properties led to the purification and characterization of a protein, named bouganin, which exhibits typical characteristics of type 1 ribosome-inactivating proteins (RIPs). Beyond that, bouganin has some peculiarities, such as a higher activity on DNA with respect to ribosomal RNA, low systemic toxicity, and immunological properties quite different than other RIPs. The sequencing of bouganin and the knowledge of its three-dimensional structure allowed to obtain a not immunogenic mutant of bouganin. These features make bouganin a very attractive tool as a component of immunotoxins (ITs), chimeric proteins obtained by linking a toxin to a carrier molecule. Bouganin-containing ITs showed very promising results in the experimental treatment of both hematological and solid tumors, and one bouganin-containing IT has entered Phase I clinical trial. In this review, we summarize the milestones of the research on bouganin such as bouganin chemico-physical characteristics, the structural properties and de-immunization studies. In addition, the in vitro and in vivo results obtained with bouganin-containing ITs are summarized
Recensioni
No full textPaolo Torresan, Intelligenze e didattica delle lingue di Mario Polito;Renate N. Caine, Geoffrey Caine, Carol L. McClintic, Karl J. Klimek, Brain/Mind Learning Principles in Action: The Fieldbook for Making Connections, Teaching, and the Human Brain di Giuseppe Longo;Claude Dubar, La socialisation. Construction des identités sociales et professionelles di Elena Zambianchi;Marc Jeannerod, Motor Cognition. What actions tell the self di Patrizia Tortella;Massimo Baldacci, La dimensione emozionale del curricolo.L’educazione affettiva razionale nella scuola di Cristiano Chiuss
Toxin and Immunotoxin Based Therapeutic Approaches
No full textIn 1900, Paul Ehrlich, who was studying ricin and abrin at the time, discovered antibodies and paved the way for immunotherapy. After 120 years, Ehrlich’s insight into the therapeutic potential of immunotargeting is still a source of inspiration for many scientists. One of the most studied antibody-based targeting strategies is the carrying of powerful toxins. The generated molecules are immunotoxins, i.e., chimeric proteins obtained by coupling bacterial or plant toxins and antibodies through chemical linking or genetic engineering. Immunotoxins are functionally designed to eliminate the cells responsible for pathological conditions, and they find applications in several fields, ranging from cancer to immunological diseases or pain control. Despite the lack of specificity, even native toxins find clinical application, but the use of unconjugated toxins is limited to loco-regional treatments.
A fundamental requirement for the medical application of toxins and their immunoconjugates is in-depth knowledge of their interaction with target cells in terms of binding, uptake, intracellular routing, and substrate specificity
Recensioni
No full textPaolo Torresan, Intelligenze e didattica delle lingue di Mario Polito;
Renate N. Caine, Geoffrey Caine, Carol L. McClintic, Karl J. Klimek, Brain/Mind Learning Principles in Action: The Fieldbook for Making Connections, Teaching, and the Human Brain di Giuseppe Longo;
Claude Dubar, La socialisation. Construction des identités sociales et professionelles di Elena Zambianchi;
Marc Jeannerod, Motor Cognition. What actions tell the self di Patrizia Tortella;
Massimo Baldacci, La dimensione emozionale del curricolo.
L’educazione affettiva razionale nella scuola di Cristiano Chiuss
Heterophyllin: A New Adenia Toxic Lectin with Peculiar Biological Properties
No full textRibosome-inactivating proteins (RIPs) are plant toxins that were identified for their ability to irreversibly damage ribosomes, thereby causing arrest of protein synthesis and induction of cell death. The RIPs purified from Adenia plants are the most potent ones. Here, we describe a novel toxic lectin from Adenia heterophylla caudex, which has been named heterophyllin. Heterophyllin shows the enzymatic and lectin properties of type 2 RIPs. Interestingly, in immunoreactivity experiments, heterophyllin poorly cross-reacts with sera against all other tested RIPs. The cytotoxic effects and death pathways triggered by heterophyllin were investigated in three human-derived cell lines: NB100, T24, and MCF7, and compared to ricin, the most known and studied type 2 RIP. Heterophyllin was able to completely abolish cell viability at nM concentration. A strong induction of apoptosis, but not necrosis, and the involvement of oxidative stress and necroptosis were observed in all the tested cell lines. Therefore, the enzymatic, immunological, and biological activities of heterophyllin make it an interesting molecule, worthy of further in-depth analysis to verify its possible pharmacological application
High in Vitro Anti-Tumor Efficacy of Dimeric Rituximab/Saporin-S6 Immunotoxin
No full textThe anti-CD20 mAb Rituximab has revolutionized lymphoma therapy, in spite of a number of unresponsive or relapsing patients. Immunotoxins, consisting of toxins coupled to antibodies, are being investigated for their potential ability to augment Rituximab efficacy. Here, we compare the anti-tumor effect of high- and low-molecular-weight Rituximab/saporin-S6 immunotoxins, named HMW-IT and LMW-IT, respectively. Saporin-S6 is a potent and stable plant enzyme belonging to ribosome-inactivating proteins that causes protein synthesis arrest and consequent cell death. Saporin-S6 was conjugated to Rituximab through an artificial disulfide bond. The inhibitory activity of HMW-IT and LMW-IT was evaluated on cell-free protein synthesis and in two CD20+ lymphoma cell lines, Raji and D430B. Two different conjugates were separated on the basis of their molecular weight and further characterized. Both HMW-IT (dimeric) and LMW-IT (monomeric) maintained a high level of enzymatic activity in a cell-free system. HMW-IT, thanks to a higher toxin payload and more efficient antigen capping, showed stronger in vitro anti-tumor efficacy than LMW-IT against lymphoma cells. Dimeric HMW-IT can be used for lymphoma therapy at least for ex vivo treatments. The possibility of using HMW-IT augments the yield in immunotoxin preparation and allows the targeting of antigens with low internalization rates
The fundamental contribution of prof. Stirpe (and his research group) to the broadening of the scientific perspective on xanthine oxidoreductase
No full textHuman xanthine oxidoreductase (XOR) is a multilevel regulated enzyme, which has many physiological functions, but which is also involved in several pathological processes. The contributions of Stirpe and his research group at the University of Bologna, to the development of knowledge on the XOR enzyme and its implications in physiological and pathological processes made a breakthrough in this field. Furthermore, their pioneering results paved the way for many research lines that are still actual and that have relevant clinical implications
Gender Influence on XOR Activities and Related Pathologies: A Narrative Review
No full textTaking into account the patient’s gender is the first step towards more precise and egalitarian medicine. The gender-related divergences observed in purine catabolism and their pathological consequences are good examples of gender medicine differences. Uric acid is produced by the activity of xanthine oxidoreductase (XOR). The serum levels of both XOR activity and uric acid differ physiologically between the genders, being higher in men than in women. Their higher levels have been associated with gout and hypertension, as well as with vascular, cardiac, renal, and metabolic diseases. The present review analyzes the gender-related differences in these pathological conditions in relation to increases in the serum levels of XOR and/or uric acid and the opportunity for gender-driven pharmacological treatment
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