Aptamers: A Review of Their Chemical Properties and Modifications for Therapeutic Application

Adachi, Tatsuo; Nakamura, Yoshikazu

doi:10.3390/molecules24234229

Cited by 217 publications

(155 citation statements)

References 114 publications

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“…In that regards, one of the latest trends in oncotherapy is the use of aptamers, representing one of the most promising compounds able to speci cally target tumor markers [60][61][62]. They are single-stranded oligonucleotides that, resembling antibodies, utilize their tridimensional shape for target recognition [63,64]. Active tumor targeting by aptamers, while preserving a nity and speci city similar to mAbs, presents several advantages over them, including smaller size, higher stability, cheaper cost for synthesis, minimal inter-batch variability and lack of immunogenicity [61,[65][66][67].…”

Section: Discussionmentioning

confidence: 99%

Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer

Camorani

Passariello

Agnello

et al. 2020

Preprint

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Background: Triple-negative breast cancer (TNBC) is a uniquely aggressive cancer with high rates of relapse due to resistance to chemotherapy. TNBC expresses higher levels of programmed cell death-ligand 1 (PD-L1) compared to other breast cancers, providing the rationale for the recently approved immunotherapy with anti-PD-L1 monoclonal antibodies (mAbs). A huge effort is dedicated to identify actionable biomarkers allowing for combination therapies with immune-checkpoint blockade. Platelet-derived growth factor receptor β (PDGFRβ) is highly expressed in invasive TNBC, both on tumor cells and tumor microenvironment. We recently proved that tumor growth and lung metastases are impaired in mouse models of human TNBC by a high efficacious PDGFRβ aptamer. Hence, we aimed at investigating the effectiveness of a novel combination treatment with the PDGFRβ aptamer and anti-PD-L1 mAbs in TNBC.Methods: The targeting ability of the anti-human PDGFRβ aptamer toward the murine receptor was verified by streptavidin-biotin assays and confocal microscopy, and its inhibitory function by transwell migration assays. The anti-proliferative effects of the PDGFRβ aptamer/anti-PD-L1 mAbs combination was assessed in human MDA-MB-231 and murine 4T1 TNBC cells, both grown as monolayer or co-cultured with lymphocytes. Tumor cell lysis and cytokines secretion by lymphocytes were analyzed by LDH quantification and ELISA, respectively. Orthotopic 4T1 xenografts in syngeneic mice were used for dissecting the effect of aptamer/mAb combination on tumor growth, metastasis and lymphocytes infiltration. Ex vivo analyses through immunohistochemistry, RT-qPCR and immunoblotting were performed. Results: We show that the PDGFRβ aptamer potentiates the anti-proliferative activity of anti-PD-L1 mAbs on both human and murine TNBC cells, according to its human/mouse cross-reactivity. Further, by binding to activated human and mouse lymphocytes, the aptamer enhances the anti-PD-L1 mAb-induced cytotoxicity of lymphocytes against tumor cells. Importantly, the aptamer heightens the antibody efficacy in inhibiting tumor growth and lung metastases in mice. It acts on both tumor cells, inhibiting Akt and ERK1/2 signaling pathways, and immune populations, increasing intratumoral CD8+T cells and reducing FOXP3+Treg cells. Conclusion: Co-treatment of PDGFRβ aptamer with anti-PD-L1 mAbs is a viable strategy, thus providing for the first an evidence of the efficacy of PDGFRβ/PD-L1 co-targeting combination therapy in TNBC.

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Section: Discussionmentioning

confidence: 99%

Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer

Camorani

Passariello

Agnello

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In that regards, one of the latest trends in oncotherapy is the use of aptamers, representing one of the most promising compounds able to speci cally target tumor markers [59][60][61]. They are single-stranded oligonucleotides that, resembling antibodies, utilize their tridimensional shape for target recognition [62,63]. Active tumor targeting by aptamers, while preserving a nity and speci city similar to mAbs, presents several advantages over them, including smaller size, higher stability, cheaper cost for synthesis, minimal inter-batch variability and lack of immunogenicity [60,[64][65][66].…”

Section: Discussionmentioning

confidence: 99%

Aptamer Targeted Therapy Potentiates Immune Checkpoint Blockade in Triple-Negative Breast Cancer

Camorani

Passariello

Agnello

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Triple-negative breast cancer (TNBC) is a uniquely aggressive cancer with high rates of relapse due to resistance to chemotherapy, the current major option for treatment. TNBC expresses higher levels of programmed cell death-ligand 1 (PD-L1) compared to other breast cancers, providing the rationale for the recently approved immunotherapy with anti-PD-L1 monoclonal antibodies (mAbs). A huge effort is dedicated to identify actionable biomarkers that may allow for novel combination therapies with immune-checkpoint blockade in TNBC. Platelet-derived growth factor receptor β (PDGFRβ) is highly expressed in mesenchymal invasive TNBC, both on tumor cells and tumor microenvironment (TME). We recently proved that tumor growth and lung metastases are impaired in mouse models of human TNBC by a high efficacious PDGFRβ aptamer. Hence, we aimed at investigating the effectiveness of a novel combination treatment with the PDGFRβ aptamer and anti-PD-L1 mAbs in TNBC.Methods: The targeting ability of the anti-human PDGFRβ aptamer toward the murine receptor was verified by streptavidin-biotin assays and confocal microscopy, and its inhibitory function by transwell migration assays on PDGFRβ-positive cells. The anti-proliferative effects of the PDGFRβ aptamer/anti-PD-L1 mAbs combination was assessed in human MDA-MB-231 and murine 4T1 TNBC cells, both grown as monolayer or co-cultured with lymphocytes. Tumor cell lysis and cytokines secretion by lymphocytes were analyzed by LDH quantification and ELISA, respectively. Orthotopic 4T1 xenografts in syngeneic mice were used for dissecting the effect of aptamer/mAbs combination on tumor growth, metastasis and lymphocytes infiltration. Ex vivo analyses through immunohistochemistry, RT-qPCR and immunoblotting were performed. Results: We show that the PDGFRβ aptamer potentiates the anti-proliferative activity of anti-PD-L1 mAbs on both human and murine TNBC cells, according to its human/mouse cross-reactivity. Further, by binding to activated human and mouse lymphocytes, the aptamer enhances the anti-PD-L1 mAbs-induced cytotoxicity of lymphocytes against tumor cells. Importantly, the aptamer heightens the antibody efficacy in inhibiting tumor growth and lung metastases in a syngeneic mouse model by acting on both TME and cancer cells. Conclusion: Co-treatment of PDGFRβ aptamer with anti-PD-L1 mAbs is a viable strategy, thus providing for the first an evidence of the efficacy of PDGFRβ/PD-L1 co-targeting combination therapy in TNBC.

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“…However, post-selection modifications can be applied to aptamers if the three-dimensional structure and binding properties are preserved [ 36 ]. Many strategies have already been developed to improve one or more aptamer properties, such as affinity, nuclease resistance, bioavailability, or thermal stability [ 37 , 38 ].…”

Section: Aptamersmentioning

confidence: 99%

Aptamers: Novel Therapeutics and Potential Role in Neuro-Oncology

Amero

Khatua

Rodríguez-Aguayo

et al. 2020

Cancers

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A relatively new paradigm in cancer therapeutics is the use of cancer cell–specific aptamers, both as therapeutic agents and for targeted delivery of anticancer drugs. After the first therapeutic aptamer was described nearly 25 years ago, and the subsequent first aptamer drug approved, many efforts have been made to translate preclinical research into clinical oncology settings. Studies of aptamer-based technology have unveiled the vast potential of aptamers in therapeutic and diagnostic applications. Among pediatric solid cancers, brain tumors are the leading cause of death. Although a few aptamer-related translational studies have been performed in adult glioblastoma, the use of aptamers in pediatric neuro-oncology remains unexplored. This review will discuss the biology of aptamers, including mechanisms of targeting cell surface proteins, various modifications of aptamer structure to enhance therapeutic efficacy, the current state and challenges of aptamer use in neuro-oncology, and the potential therapeutic role of aptamers in pediatric brain tumors.

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Aptamers: A Review of Their Chemical Properties and Modifications for Therapeutic Application

Cited by 217 publications

References 114 publications

Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer

Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer

Aptamer Targeted Therapy Potentiates Immune Checkpoint Blockade in Triple-Negative Breast Cancer

Aptamers: Novel Therapeutics and Potential Role in Neuro-Oncology

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