Anything You Can Do, I Can Do Better: Can Aptamers Replace Antibodies in Clinical Diagnostic Applications?

Bauer, Michelle J; Strom, Mia; Hammond, David S.; Shigdar, Sarah

doi:10.3390/molecules24234377

Cited by 83 publications

(73 citation statements)

References 79 publications

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“…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]. While aptamers are generally functionalized with cytotoxic payloads for cancer therapy, it has been also demonstrated their ability to be antagonistic agents independent of drug conjugation, exerting signi cant potential as anti-cancer therapeutics [31,37,68].…”

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

“…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]. While aptamers are generally functionalized with cytotoxic payloads for cancer therapy, it has been also demonstrated their ability to be antagonistic agents independent of drug conjugation, exerting signi cant potential as anti-cancer therapeutics [31,37,67].…”

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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“…The main stay in human disease research over the past 40 years has been monoclonal antibodies [52]. These have proven to be very effective in diagnostic applications where the antibody has been fully validated and quality controls are in place to ensure each batch of antibody performs to the strict requirements [53]. However, in research applications there have been several limitations, notwithstanding the reproducibility crisis that has been placed at the feet of reagents, and antibodies in particular, in a high percentage of cases [54].…”

Section: Towards a Better System Of Detecting Proteome Signaturesmentioning

confidence: 99%

“…Going back to the protein nature of antibodies and nanobodies, these require special conditions to be used in the field for POCT. For example, transport needs to be refrigerated and antibodies/nanobodies need to be kept cool to ensure they remain functional, whereas aptamers are stable at higher temperatures [53,100]. Additionally, while aptamers have been used to replace antibodies in typical laboratory tests, they have also come into their own in a number of in vitro diagnostic assays that would be easily adapted to in field or POCT [101][102][103][104].…”

Section: In Vitro Applications: Which Is Best?mentioning

confidence: 99%

Antibodies, Nanobodies, or Aptamers—Which Is Best for Deciphering the Proteomes of Non-Model Species?

Dhar

Samarasinghe

Shigdar

2020

IJMS

Self Cite

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This planet is home to countless species, some more well-known than the others. While we have developed many techniques to be able to interrogate some of the “omics”, proteomics is becoming recognized as a very important part of the puzzle, given how important the protein is as a functional part of the cell. Within human health, the proteome is fairly well-established, with numerous reagents being available to decipher cellular pathways. Recent research advancements have assisted in characterizing the proteomes of some model (non-human) species, however, in many other species, we are only just touching the surface. This review considers three main reagent classes—antibodies, aptamers, and nanobodies—as a means of continuing to investigate the proteomes of non-model species without the complications of understanding the full protein signature of a species. Considerations of ease of production, potential applications, and the necessity for producing a new reagent depending on homology are presented.

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Anything You Can Do, I Can Do Better: Can Aptamers Replace Antibodies in Clinical Diagnostic Applications?

Cited by 83 publications

References 79 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

Antibodies, Nanobodies, or Aptamers—Which Is Best for Deciphering the Proteomes of Non-Model Species?

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