A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect

Huang, Bo; Lai, Wei-Yun; Chang, Yi; Wang, Jen Wei; Yeh, Shauh Der; Lin, Emily

doi:10.1016/j.omtn.2017.08.006

Cited by 52 publications

(28 citation statements)

References 54 publications

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“…Monoclonal antibodies targeting cytotoxic T lymphocyte antigen-4 (CTLA-4) and PD-1/PD-L1 axis are now a part of routine clinical practice [ 168 ]. Huang et al reported a novel high-affinity CTLA-4-antagonizing DNA aptamer that promoted lymphocyte proliferation and inhibited tumor growth in a murine syngeneic tumor model with mouse TC-1 lung cancer cells [ 146 ].…”

Section: Aptamers As Therapeutics Under Investigation In Oncologymentioning

confidence: 99%

Aptamer Therapeutics in Cancer: Current and Future

Morita

Leslie

Kameyama

et al. 2018

Cancers

164

112

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Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small—approximately one-tenth that of monoclonal antibodies—their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules. Additionally, unlike antibodies, aptamers can be readily chemically synthesized and modified. In addition, aptamers’ long storage period and low immunogenicity are favorable properties for clinical utility. Due to their flexibility of chemical modification, aptamers are conjugated to other chemical entities including chemotherapeutic agents, siRNA, nanoparticles, and solid phase surfaces for therapeutic and diagnostic applications. However, as relatively small sized oligonucleotides, aptamers present several challenges for successful clinical translation. Their short plasma half-lives due to nuclease degradation and rapid renal excretion necessitate further structural modification of aptamers for clinical application. Since the US Food and Drug Administration (FDA) approval of the first aptamer drug, Macugen® (pegaptanib), which treats wet-age-related macular degeneration, several aptamer therapeutics for oncology have followed and shown promise in pre-clinical models as well as clinical trials. This review discusses the advantages and challenges of aptamers and introduces therapeutic aptamers under investigation and in clinical trials for cancer treatments.

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Section: Aptamers As Therapeutics Under Investigation In Oncologymentioning

confidence: 99%

Aptamer Therapeutics in Cancer: Current and Future

Morita

Leslie

Kameyama

et al. 2018

Cancers

164

112

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“…The elucidation of critical molecular targets, such as immune checkpoints or immunostimulatory targets, opens the opportunities to develop immunotherapy by targeting these molecular sites. A variety of aptamers have been developed for immune checkpoints that are involved in immune suppression in cancer patients, such as programmed death receptor I (PD-1) or its ligand programmed death ligand I (PD-L1), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and T cell immunoglobulin-3 (TIM-3) [68, 69, 71–76, 170]. By molecular engineering of these aptamers with immunotherapeutics, ApDCs can be developed for specific delivery of immunotherapeutics.…”

Section: Aptamer-drug Conjugates (Apdcs) For Targeted Drug Deliverymentioning

confidence: 99%

“…As mentioned above, aptamers can also serve as immunotherapeutics themselves (Figure 5A). In the context of cancer immunotherapy, therapeutic aptamers have been reported for immune checkpoints such as CTLA-4, PD-1, PD-L1, and Tim-3 for tumor immunotherapy [68, 69, 72–76, 170]. Given the unique features of aptamer therapeutics in terms of screening, manufacture, stability, as well as fast tissue penetration, aptamer inhibitors of immune checkpoints provide unique opportunities to develop cancer immunotherapy as an alternative to the current mainstream of antibody therapeutics.…”

Section: Aptamer-drug Conjugates (Apdcs) For Targeted Drug Deliverymentioning

confidence: 99%

Aptamer-based targeted therapy

Zhu

Chen

2018

Advanced Drug Delivery Reviews

331

216

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Precision medicine holds great promise to harness genetic and epigenetic cues for targeted treatment of a variety of diseases, ranging from many types of cancers, neurodegenerative diseases, to cardiovascular diseases. The proteomic profiles resulting from the unique genetic and epigenetic signatures represent a class of relatively well accessible molecular targets for both interrogation (e.g., diagnosis, prognosis) and intervention (e.g., targeted therapy) of these diseases. Aptamers are promising for such applications by specific binding with cognate disease biomarkers. Nucleic acid aptamers are a class of DNA or RNA with unique three-dimensional conformations that allow them to specifically bind with target molecules. Aptamers can be relatively easily screened, reproducibly manufactured, programmably designed, and chemically modified for various biomedical applications, including targeted therapy. Aptamers can be chemically modified to resist enzymatic degradation or optimize their pharmacological behaviors, which ensured their chemical integrity and bioavailability under physiological conditions. In this review, we will focus on recent progress and discuss the challenges and opportunities in the research areas of aptamer-based targeted therapy in the forms of aptamer therapeutics and aptamer-drug conjugates (ApDCs).

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“…The anti-CTLA4 DNA aptamer significantly stimulated the activation of T lymphocytes for antitumor defense in in vitro and in in vivo studies [83]. CTLA4 (cytotoxic T lymphocyte-associated protein 4) belongs to immune checkpoints and is responsible for the inhibition of excessive activation of T lymphocytes recruited in lymph nodes [84].…”

Section: Aptamers In Nsclc Treatmentmentioning

confidence: 99%

Aptamers in Non-Small Cell Lung Cancer Treatment

2020

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Aptamers are short, single-stranded oligonucleotides which are capable of specifically binding to single molecules and cellular structures. Aptamers are also known as “chemical antibodies”. Compared to monoclonal antibodies, they are characterized by higher reaction specificity, lower molecular weight, lower production costs, and lower variability in the production stage. Aptamer research has been extended during the past twenty years, but only Macugen® has been accepted by the Food and Drug Administration (FDA) to date, and few aptamers have been examined in clinical trials. In vitro studies with aptamers have shown that they may take part in the regulation of cancer progression, angiogenesis, and metastasis processes. In this article, we focus on the potential use of aptamers in non-small cell lung cancer treatment.

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A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect

Cited by 52 publications

References 54 publications

Aptamer Therapeutics in Cancer: Current and Future

Aptamer Therapeutics in Cancer: Current and Future

Aptamer-based targeted therapy

Aptamers in Non-Small Cell Lung Cancer Treatment

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