In vivo targeting and growth inhibition of the A20 murine B-cell lymphoma by an idiotype-specific peptide binder

Palmieri, Camillo; Falcone, Cristina; Iaccino, Enrico; Tuccillo, Franca Maria; Gaspari, Marco; Trimboli, Francesca; Laurentiis, Annamaria de; Luberto, Laura; Pontoriero, Marilena; Pisano, Antonio; Vecchio, Eleonora; Fierro, Olga; Panico, Mariarosaria; Larobina, Michele; Gargiulo, Sara; Costa, Nicola; Piaz, Fabrizio Dal; Schiavone, Marco; Arra, Claudio; Giudice, Aldo; Palma, Giuseppe; Barbieri, Antônio; Quinto, Ileana; Scala, Giuseppe

doi:10.1182/blood-2009-11-253617

Cited by 33 publications

(44 citation statements)

References 43 publications

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“…It pathologically mimics the characteristics of human diffuse large B-cell lymphoma. 29,34 The 5T33 murine myeloma (5T33MM) cells were used as control. The cell lines were kindly provided by Prof C Palmieri (University of Catanzaro, Italy).…”

Section: Cells and Reagentsmentioning

confidence: 99%

“…41,42 To further confirm the specificity of pA2036-modified DNPs in targeting A20 cells, the nanoparticle uptake of A20 cells was compared with that of 5T33MM cells, a surface IgG-positive B-cell line unable to bind the pA2036 peptide ( Figure 2H). 29 The fluorescent cell population of mildly permeabilized 5T33MM cells treated with DNPs•pA2036* was approximately threefold lower than that of A20 cells (34%±3% vs 96%±4%). These data, together with that obtained using DNPs•pRND*, indicate that a portion of DNPs•pA2036* nanoparticles were nonspecifically internalized by the cells.…”

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confidence: 99%

“…29 As a ligand of the idiotypic determinants of the Ig-BCR, the specificity of each Id-peptide is strongly restricted to a specific B-cell clone (normal or neoplastic) that harbors the cognate Ig-BCR.…”

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confidence: 99%

“…27,28 In this study, an active targeting strategy for Bcl2 siRNA delivery was developed to specifically target extremely aggressive murine A20 lymphoma cells, using as ligand an idiotype-specific peptide (Id-peptide) endowed with high affinity toward B-cell receptor (BCR, homing device). 29,30 The idiotype determinants of the immunoglobulin B-cell receptor (Ig-BCR) of B-cell malignancies are unique for a given clonal population and function as patient-specific tumor antigen that may be exploited for active therapeutic targeting in personalized cancer therapy. 30 The choice of Idpeptides was based on the following properties: 1) binding to tumor target cells with high specificity and sensitivity, both in vitro and in vivo, and 2) internalization into target tumor cells by BCR-mediated endocytosis, which overcomes drug resistance.…”

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confidence: 99%

“…30 The choice of Idpeptides was based on the following properties: 1) binding to tumor target cells with high specificity and sensitivity, both in vitro and in vivo, and 2) internalization into target tumor cells by BCR-mediated endocytosis, which overcomes drug resistance. [29][30][31] Based on these considerations, diatomite nanoparticles (DNPs) conjugated with an Id-peptide and loaded with siRNA directed against Bcl2, highly expressed in most B-cell lymphomas, were explored as a ligand-mediated delivery platform.…”

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confidence: 99%

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Nanoparticle-based strategy for personalized B-cell lymphoma therapy

Martucci¹,

Migliaccio²,

Ruggiero³

et al. 2016

IJN

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B-cell lymphoma is associated with incomplete response to treatment, and the development of effective strategies targeting this disease remains challenging. A new personalized B-cell lymphoma therapy, based on a site-specific receptor-mediated drug delivery system, was developed in this study. Specifically, natural silica-based nanoparticles (diatomite) were modified to actively target the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2) with small interfering RNA (siRNA). An idiotype-specific peptide (Id-peptide) specifically recognized by the hypervariable region of surface immunoglobulin B-cell receptor was exploited as a homing device to ensure specific targeting of lymphoma cells. Specific nanoparticle uptake, driven by the Id-peptide, was evaluated by flow cytometry and confocal microscopy and was increased by approximately threefold in target cells compared with nonspecific myeloma cells and when a random control peptide was used instead of Id-peptide. The specific internalization efficiency was increased by fourfold when siRNA was also added to the modified nanoparticles. The modified diatomite particles were not cytotoxic and their effectiveness in downregulation of gene expression was explored using siRNA targeting Bcl2 and evaluated by quantitative real-time polymerase chain reaction and Western blot analyses. The resulting gene silencing observed is of significant biological importance and opens new possibilities for the personalized treatment of lymphomas

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Section: Cells and Reagentsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Nanoparticle-based strategy for personalized B-cell lymphoma therapy

Martucci¹,

Migliaccio²,

Ruggiero³

et al. 2016

IJN

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Physician finds volunteer work rewarding

Printz¹

2011

Cancer

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Receptor‐targeted therapies have become standard in the treatment of various lymphomas. In view of its unparalleled specificity for the malignant B‐cell clone, the B‐cell receptor (BCR) on B cell lymphoma cells is a potential therapeutic target. We have used two BCR epitope mimicking peptides binding to the Burkitt's lymphoma cell lines CA46 and SUP‐B8. We proved their functionality by demonstrating calcium flux and BCR‐mediated endocytosis upon peptide receptor binding. Toxicity experiments in vitro via cross‐linking of the BCR with tetramerized epitope mimics lead to apoptosis in both cell lines but was far more effective in SUP‐B8 cells. We established a SUP‐B8‐based disseminated Burkitt's lymphoma model in NOD/SCID mice. Treatment of tumor‐bearing mice with tetramerized epitope mimics had significant anti‐tumor effects in vivo. We conclude that peptide‐mediated, BCR‐targeted therapy is a promising approach which may be explored and further developed for application in highly aggressive lymphoma.

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