Aptamer TY04 inhibits the growth of multiple myeloma cells via cell cycle arrest

Dai, Heping; Ye, Mao; Peng, Man; Zhou, Weihua; Bai, Huarong; Xiao, Xiaojuan; Ma, Bian-Ying; Zhou, Jiajie; Tang, Shijun; Yao, Shanshan; Cao, Ye; Qin, Zhiqiang; Liu, Jing; Tan, Weihong

doi:10.1007/s13277-014-1920-2

Cited by 6 publications

(3 citation statements)

References 19 publications

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“…However, aptamers are advantageous over antibodies due to their low potential for immunogenicity, efficient tissue penetration, relatively simple synthesis, etc . To date, a small number of aptamers have been developed as therapeutic antagonists in MM, but none target c‐met.…”

Section: Introductionmentioning

confidence: 99%

Targeting c‐met receptor tyrosine kinase by the DNA aptamer SL1 as a potential novel therapeutic option for myeloma

Zhang

Gao

Zhou

et al. 2018

J Cellular Molecular Medi

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Hepatocyte growth factor (HGF)/c‐met pathway activation has been implicated in the pathogenesis of multiple myeloma (MM), and blocking this pathway has been considered a rational therapeutic strategy for treating MM. Aptamers are single‐stranded nucleic acid molecules that fold into complex 3D structures and bind to a variety of targets. Recently, it was reported that DNA aptamer SL1 exhibited high specificity and affinity for c‐met and inhibited HGF/c‐met signaling in SNU‐5 cells. However, as the first c‐met‐targeted DNA aptamer to be identified, application of SL1 to myeloma treatment requires further investigation. Here, we explore the potential application of SL1 in MM. Our results indicated that c‐met expression is gradually increased in MM patients and contributes to poor outcomes. SL1 selectively bound to c‐met‐positive MM cells but not to normal B cells and suppressed the growth, migration and adhesion of MM cells in vitro in a co‐culture model performed with HS5 cells, wherein SL1 inhibited HGF‐induced activation of c‐met signaling. In vivo and ex vivo fluorescence imaging showed that SL1 accumulated in the c‐met positive tumour areas. In addition, SL1 was active against CD138+ primary MM cells and displayed a synergistic inhibition effect with bortezomib. Collectively, our data suggested that SL1 could be beneficial as a c‐met targeted antagonist in MM.

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Section: Introductionmentioning

confidence: 99%

Targeting c‐met receptor tyrosine kinase by the DNA aptamer SL1 as a potential novel therapeutic option for myeloma

Zhang

Gao

Zhou

et al. 2018

J Cellular Molecular Medi

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“…Unlike nanobodies, their use is not impaired by the batch-to-batch variability affecting the antibody drugs in general. To date, only a few aptamers have proven useful in targeting proteins on the surface of aberrant plasma cell lines, such as TY04, annexin A2-binding aptamer, SL1 against tyrosine-protein kinase Met, and, more recently, apt69.T against BCMA [ 113 , 114 , 115 , 116 ]. In this case, too, further interdisciplinary efforts are necessary to move this innovative, sophisticated approach from bench to bedside.…”

Section: Overcoming the Newest: From The Microscopic To The Nanoscopi...mentioning

confidence: 99%

Race for the Cure: From the Oldest to the Newest Monoclonal Antibodies for Multiple Myeloma Treatment

2022

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Multiple myeloma is characterized by a wide clinical heterogeneity due to an intricate network of interactions between bone marrow-resident clonal plasma cells and the microenvironment. Over the last years, dramatic improvement in the understanding of these pathways led to the introduction of novel drugs with immune-mediated mechanisms of action. Some of these compounds, such as the anti-cd38 daratumumab and isatuximab, the anti-slamf-7 elotuzumab, and the antibody-drug conjugate belantamab-mafodotin, have been tested in large clinical trials and have now fully entered the real-life management. The bispecific T-cell engagers are under investigation with promising results, and other satisfactory data is expected from the application of nanotechnologies. The perfect timing to introduce these drugs in the sequence of treatment and their adverse events represent new challenges to be addressed, and further experience is required to improve their use.

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“…36 In contrast to antibodies, aptamers can bind to hundreds of molecules of different sizes and structures without compromising immune response. To date, many aptamer targets have been identified, including cocaine, 37,38 growth factors, [39][40][41] peptides, 42,43 toxins, 44,45 viral proteins, 46,47 even live cells and tissues, [48][49][50][51] most of which were performed successfully under controlled aptamer selection and translated into clinical practice.…”

Section: Non-immunogenic and Nontoxic With Broad Target Selectionmentioning

confidence: 99%

Advances in the development of aptamer drug conjugates for targeted drug delivery

Chen

Liu

et al. 2016

WIREs Nanomed Nanobiotechnol

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A key goal of modernmedicine is target-specific therapeutic intervention.However, most drugs lackselectivity, resulting in“off-target” side effects.To address the requirements of “targeted therapy,”aptamers, which are artificial oligonucleotides,have beenusedas novel targeting ligands to construct aptamer drug conjugates (ApDC)that can specifically bind to a broad spectrum of targets, including diseased cells. Accordingly, the applicationof aptamers in targeted drug delivery has attracted broad interest due to their impressive selectivity and affinity, low immunogenicity, easy synthesis with high reproducibility, facile modification, and relatively rapid tissue penetration with no toxicity. Functionally, aptamers themselves can be used as macromolecular drugs, and they are also commonly used in biomarker discovery and targeted drug delivery. In this review,we will highlight the most recent advances in the development of aptamers and aptamer conjugates, and discuss their potential in targeted therapy.

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Aptamer TY04 inhibits the growth of multiple myeloma cells via cell cycle arrest

Cited by 6 publications

References 19 publications

Targeting c‐met receptor tyrosine kinase by the DNA aptamer SL1 as a potential novel therapeutic option for myeloma

Targeting c‐met receptor tyrosine kinase by the DNA aptamer SL1 as a potential novel therapeutic option for myeloma

Race for the Cure: From the Oldest to the Newest Monoclonal Antibodies for Multiple Myeloma Treatment

Advances in the development of aptamer drug conjugates for targeted drug delivery

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