A new approach for the treatment of CLL using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles

Capolla, Sara; Mezzaroba, Nelly; Zorzet, Sonia; Tripodo, Claudio; Mendoza-Maldonado, Ramiro; Granzotto, Marilena; Vita, Francesca; Spretz, Ruben; Larsen, Gustavo; Noriega, Sandra; Mansilla, Eduardo; Bo, Michele Dal; Gattei, Valter; Pozzato, Gabriele; Núñez, Luis; Macor, Paolo

doi:10.1007/s12274-015-0935-3

Cited by 20 publications

(14 citation statements)

References 25 publications

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“…The presence of specific proteins in tissue samples was confirmed by western blot performed as previously described [23]. Unfixed tissue samples from Patient 12 and control C were snap-frozen and embedded in OCT medium (Diagnostic Division; Miles Inc., Elkhart, IN, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

Multiple-Organ Complement Deposition on Vascular Endothelium in COVID-19 Patients

et al. 2021

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Increased levels of circulating complement activation products have been reported in COVID-19 patients, but only limited information is available on complement involvement at the tissue level. The mechanisms and pathways of local complement activation remain unclear. The aim of this study was to investigate the deposition of complement components in the lungs, kidneys, and liver in patients with COVID-19 patients and to determine the pathway/s of complement activation. We performed immunofluorescence analyses of autopsy specimens of lungs, kidney, and liver from 12 COVID-19 patients who died of acute respiratory failure. Snap-frozen samples embedded in OCT were stained with antibodies against complement components and activation products, IgG, and spike protein of SARS-CoV-2. Lung deposits of C1q, C4, C3, and C5b-9 were localized in the capillaries of the interalveolar septa and on alveolar cells. IgG displayed a similar even distribution, suggesting classical pathway activation. The spike protein is a potential target of IgG, but its uneven distribution suggests that other viral and tissue molecules may be targeted by IgG. FB deposits were also seen in COVID-19 lungs and are consistent with activation of the alternative pathway, whereas MBL and MASP-2 were hardly detectable. Analysis of kidney and liver specimens mirrored findings observed in the lung. Complement deposits were seen on tubules and vessels of the kidney with only mild C5b-9 staining in glomeruli, and on the hepatic artery and portal vein of the liver. Complement deposits in different organs of deceased COVID-19 patients caused by activation of the classical and alternative pathways support the multi-organ nature of the disease and the contribution of the complement system to inflammation and tissue damage.

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Section: Western Blot Analysismentioning

confidence: 99%

Multiple-Organ Complement Deposition on Vascular Endothelium in COVID-19 Patients

et al. 2021

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“…To overcome some of the limitations of standard anticancer drugs, they can be encapsulated inside biodegradable polymeric NPs which guarantees the delivery of the drug to the target site and a continuous and controlled release. Chlorambucil and hydroxychloroquine [ 110 – 112 ] or doxorubicin [ 113 ] are loaded inside biodegradable polymeric NPs and are functionalized with anti-CD20 or anti-CD19 antibodies to specifically target different neoplastic B-cells. Idarubicin, an anthracycline antibiotic approved by FDA analogue to daunorubicin, can be encapsulated in methoxy poly(ethylene glycol)-b-poly(l-lactide-co-glycolide) nanoparticles [ 114 ].…”

Section: Nanoparticle-based Therapymentioning

confidence: 99%

Nanoparticles for hematologic diseases detection and treatment

2019

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Nanotechnology, as an interdisciplinary science, combines engineering, physics, material sciences, and chemistry with the biomedicine knowhow, trying the management of a wide range of diseases. Nanoparticle-based devices holding tumor imaging, targeting and therapy capabilities are formerly under study. Since conventional hematological therapies are sometimes defined by reduced selectivity, low therapeutic efficacy and many side effects, in this review we discuss the potential advantages of the NPs’ use in alternative/combined strategies. In the introduction the basic notion of nanomedicine and nanoparticles’ classification are described, while in the main text nanodiagnostics, nanotherapeutics and theranostics solutions coming out from the use of a wide-ranging NPs availability are listed and discussed.

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“…It is important to point out that tumor cells are often heterogeneous in the expression level of tumor antigens that may influence their susceptibility to CDC. We have observed that cells expressing low levels of CD20 isolated by cell sorting from a population of either chronic lymphocytic leukemia (CLL) or cancer B-cell lines and kept in culture for over a week give rise to cells expressing higher level of CD20 that more easily undergo C-mediated lysis ( 40 , 41 ). This observation suggests that repeated injections of Abs administered at appropriate time intervals can be used to allow the emergence of cell clones expressing higher levels of CD20 and more susceptible to CDC.…”

Section: Factors Affecting the Efficiency Of The Antibodies To Activamentioning

confidence: 99%

Complement as a Biological Tool to Control Tumor Growth

2018

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Deposits of complement components have been documented in several human tumors suggesting a potential involvement of the complement system in tumor immune surveillance. In vitro and in vivo studies have revealed a double role played by this system in tumor progression. Complement activation in the cancer microenvironment has been shown to promote cancer growth through the release of the chemotactic peptide C5a recruiting myeloid suppressor cells. There is also evidence that tumor progression can be controlled by complement activated on the surface of cancer cells through one of the three pathways of complement activation. The aim of this review is to discuss the protective role of complement in cancer with special focus on the beneficial effect of complement-fixing antibodies that are efficient activators of the classical pathway and contribute to inhibit tumor expansion as a result of MAC-mediated cancer cell killing and complement-mediated inflammatory process. Cancer cells are heterogeneous in their susceptibility to complement-induced killing that generally depends on stable and relatively high expression of the antigen and the ability of therapeutic antibodies to activate complement. A new generation of monoclonal antibodies are being developed with structural modification leading to hexamer formation and enhanced complement activation. An important progress in cancer immunotherapy has been made with the generation of bispecific antibodies targeting tumor antigens and able to neutralize complement regulators overexpressed on cancer cells. A great effort is being devoted to implementing combined therapy of traditional approaches based on surgery, chemotherapy and radiotherapy and complement-fixing therapeutic antibodies. An effective control of tumor growth by complement is likely to be obtained on residual cancer cells following conventional therapy to reduce the tumor mass, prevent recurrences and avoid disabilities.

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A new approach for the treatment of CLL using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles

Cited by 20 publications

References 25 publications

Multiple-Organ Complement Deposition on Vascular Endothelium in COVID-19 Patients

Multiple-Organ Complement Deposition on Vascular Endothelium in COVID-19 Patients

Nanoparticles for hematologic diseases detection and treatment

Complement as a Biological Tool to Control Tumor Growth

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