Rituximab (anti-CD20)-modified AZD-2014-encapsulated nanoparticles killing of B lymphoma cells

Tang, Xi-can; Xie, Chao; Jiang, Zhuhua; Li, Amin; Cai, Shunyou; Chao-zhen, Hou; Wang, Jian; Ma, Dong

doi:10.1080/21691401.2018.1478844

Cited by 9 publications

(5 citation statements)

References 35 publications

(42 reference statements)

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“…The targeted therapies against CD20 are not limited to antibodies. Recently, CD20 found to be an potential receptor in nanomedicine [ 17 ] and cancer immunotherapy [ 18 ]. For instance, there are some CAR-T and NK cells under investigation for CD20 + lymphoma (7, 8).…”

Section: Introductionmentioning

confidence: 99%

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Isolation and characterization of human anti-CD20 single-chain variable fragment (scFv) from a Naive human scFv library

Shams

Nikkhoi

et al. 2022

Med Oncol

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CD20 is a receptor expressed on B cells with anonymous functions. The receptor is the target of some food and drug administration (FDA) approved monoclonal antibodies (mAb), such as Rituximab and Obinutuzumab. Blocking CD20 using the aforementioned mAbs has improved Non-Hodgkin Lymphoma (NHL) therapy. All commercial mAbs on the market were raised in non-human animal models. Antibody humanization is inevitable to mitigate immune response. In order to keep the affinity of antibody intact, humanizations are only applied to frameworks which do not eliminate immune response to foreign CDRs sequences. To address this issue, human monoclonal antibody deemed imperative. Herein, we report the isolation and characterization of a fully human single-chain variable fragment (scFv) against the large loop of CD20 from naïve human antibody library. After three rounds of phage display, a library of enriched anti-CD20 scFv was obtained. The polyclonal phage ELISA demonstrated that after each round of phage display, the population of anti-CD20 scFv became dominant. The scFv, G7, with the most robust interaction with CD20 was selected for further characterization. The specificity of G7 scFv was evaluated by ELISA, western blot, and flow cytometry. Detecting CD20 in western blot showed that G7 binds to a linear epitope on CD20 large loop. Next, G7 scFv was also bound to Raji cell (CD20 + ) while no interaction was recorded with K562 cell line (CD20 — ). This data attested that the epitope recognized by G7 scFv is accessible on the cell membrane. The affinity of G7 scFv was estimated to be 63.41 ± 3.9 nM. Next, the sensitivity was evaluated to be 2 ng/ml. Finally, G7 scFv tertiary structure was modeled using Graylab software. The 3D structure illustrated two domains of variable heavy (V H ) and variable light (V L ) connected through a linker. Afterward, G7 scFv and CD20 were applied to in-silico docking using ClusPro to illustrate the interaction of G7 with the large loop of CD20. As the selected scFv from the human antibody library is devoid of interspecies immunogenic amino acids sequences, no humanization or any other modifications are required prior to clinical applications.

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Section: Introductionmentioning

confidence: 99%

“…Traditionally, mAb used to be generated in mice, such as anti-CD3 Muromomab. However, murine-derived mAbs raised human anti-mouse antibody (HAMA) responses in some patients [ 17 ]. To address this issue, mAbs were engineered to incorporate more human sequences to alleviate side effects, which resulted in Chimeric and Humanized mAb.…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of human anti-CD20 single-chain variable fragment (scFv) from a Naive human scFv library

Shams

Nikkhoi

et al. 2022

Med Oncol

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“…Nanomaterial loading of an mTOR inhibitor inhibited the expression of 4E-BP1 in B lymphoma cells. 37 However, there is no satisfactory research on nanomaterials without contents assessing changes in 4E-BP1 levels. 4E-BP1 is a downstream effector of mTOR, 38 and its expression is higher in PCa tissue than in normal tissue.…”

Section: Discussionmentioning

confidence: 99%

<p>Carbon Nanospheres Exert Antitumor Effects Associated with Downregulation of 4E-BP1 Expression on Prostate Cancer</p>

Dong¹,

Luo²,

Zhang³

et al. 2020

IJN

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Introduction: Although carbon nanospheres (CNPs) are promising nanomaterials in cancer treatment, how they affect prostate cancer (PCa) remains unclear. Methods: In this study, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Raman spectroscopy were used to confirm the successful synthesis of CNPs. CCK-8, flow cytometry, Transwell, wound healing, Western blot and immunohistochemistry (IHC) assays were performed to evaluate the antitumor effect of CNPs toward the two kinds of prostate cancer cell lines PC3 and DU145. Results: Our results showed that CNPs inhibited cell growth, invasion, and migration and induced apoptosis and autophagy in PCa cells. Multifactor detection of a single Akt phosphorylation pathway and Western blot results suggested the suppression of 4E-BP1 in PCa cells after incubation with CNPs. The results from animal experiments also suggested the antitumor effect of CNPs and reduced 4E-BP1 expression in PCa tissue samples from BALB/ c nude mice administered a local subcutaneous injection of CNPs.

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“…Tang et al . reported a rituximab (anti-CD20)-modified AZD-2014 encapsulated nanoparticle for killing B lymphoma cells [ 220 ]. Torino et al .…”

Section: Nanomedicine Strategies Against Hmsmentioning

confidence: 99%

“…Regarding other targets, Nevala et al reported an CD20 antibody-modified paclitaxelloaded nanoparticle for the treatment of CD20 + B cell lymphoma [219]. Tang et al reported a rituximab (anti-CD20)-modified AZD-2014 encapsulated nanoparticle for killing B lymphoma cells [220]. Torino et al reported a BCR-targeted multimodal imaging-engineered nanoparticle for the therapeutic and diagnosis of B cell lymphoma [221].…”

Section: Targeting Cancer Cellsmentioning

confidence: 99%

Development and application of nanomaterials, nanotechnology and nanomedicine for treating hematological malignancies

Wang

Han

et al. 2023

J Hematol Oncol

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Hematologic malignancies (HMs) pose a serious threat to patients’ health and life, and the five-year overall survival of HMs remains low. The lack of understanding of the pathogenesis and the complex clinical symptoms brings immense challenges to the diagnosis and treatment of HMs. Traditional therapeutic strategies for HMs include radiotherapy, chemotherapy, targeted therapy and hematopoietic stem cell transplantation. Although immunotherapy and cell therapy have made considerable progress in the last decade, nearly half of patients still relapse or suffer from drug resistance. Recently, studies have emerged that nanomaterials, nanotechnology and nanomedicine show great promise in cancer therapy by enhancing drug targeting, reducing toxicity and side effects and boosting the immune response to promote durable immunological memory. In this review, we summarized the strategies of recently developed nanomaterials, nanotechnology and nanomedicines against HMs and then proposed emerging strategies for the future designment of nanomedicines to treat HMs based on urgent clinical needs and technological progress.

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Rituximab (anti-CD20)-modified AZD-2014-encapsulated nanoparticles killing of B lymphoma cells

Cited by 9 publications

References 35 publications

Isolation and characterization of human anti-CD20 single-chain variable fragment (scFv) from a Naive human scFv library

Isolation and characterization of human anti-CD20 single-chain variable fragment (scFv) from a Naive human scFv library

<p>Carbon Nanospheres Exert Antitumor Effects Associated with Downregulation of 4E-BP1 Expression on Prostate Cancer</p>

Development and application of nanomaterials, nanotechnology and nanomedicine for treating hematological malignancies

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