Cancer immunomodulation using bispecific aptamers

Thomas, Brian; Porciani, David; Burke, Donald H.

doi:10.1016/j.omtn.2022.01.008

Cited by 25 publications

(23 citation statements)

References 177 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unmodified aptamers have a circulation half-life of minutes to hours and are degraded in serum by exonucleases. The circulating half-life of GreenB1 can be extended by adding high molecular weight compounds such as poly-ethylene glycol (PEG), creating multivalent constructs larger than the glomerular filtration rate cut off (50-60 kDa) (15, 63) or circularising the aptamer to make it less susceptible to nuclease digestion (64). GreenB1 can be further linked to cytotoxic chemicals via a lysosome-sensitive linker (65) or liposomes containing an anticancer payload (66) to assess its ability to diminish tumour burden.…”

Section: Discussionmentioning

confidence: 99%

“…Their affinity and specificity are comparable to antibodies; however, aptamers are smaller (6-30 kDa versus 150-180 kDa for antibodies) and can be chemically synthesised, resulting in minimal to no batch-to-batch variability and straightforward scale-up. Aptamers are stable, can be denatured/refolded, show a rapid tissue uptake (14) and low immunogenicity (15). Recently, Kelly et al have highlighted considerable difficulties in translating aptamers selected under cell-free settings to in vitro and in vivo studies.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Targeting triple-negative breast cancer with β1-integrin binding aptamer

Pleiko

Haugas

Parfejevs

et al. 2022

Preprint

View full text Add to dashboard Cite

Targeted therapies have increased the treatment options for triple-negative breast cancer patients. However, the paucity of targetable biomarkers and tumour heterogeneity have limited the ability of precision-guided interventions to live up to their full potential. As affinity targeting ligands, aptamers show high selectivity towards target molecules. Compared to antibodies, aptamers have lower molecular weight, increased stability during transportation, reduced immunogenicity, and increased tissue uptake. Recently, we reported the discovery of GreenB1 aptamer that is internalized in cultured triple-negative MDA-MB-231 human breast cancer cells. We show that the GreenB1 aptamer specifically targets β1-integrin, a protein previously linked to breast cancer cell invasiveness and migration. Aptamer binds to β1-integrin with low nanomolar affinity. GreenB1 homes in the orthotopic 4T1 triple-negative breast cancer lesions modelled in mice. Our findings suggest potential applications for the GreenB1-guided precision agents for the diagnosis and therapy of triple-negative breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeting triple-negative breast cancer with β1-integrin binding aptamer

Pleiko

Haugas

Parfejevs

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…First, aptamers for a certain molecular target can be cost-effectively screened in vitro. Second, aptamers can be easily synthesized and manufactured in large-scale (Thomas et al 2022;Zhu and Chen 2018). Third, the stable structure of aptamers affords them a long storage period and a relatively high resistance to heat, for their tertiary structures can be quickly restored following heat denaturation (Morita et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Novel Bispecific Aptamer Targeting PD-1 and Nucleolin for Cancer Immunotherapy

Yao

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Immune checkpoint blockade (ICB) is a promising strategy for cancer treatment and has achieved remarkable clinical results. Further improvement of ICB efficacy may advance cancer immunotherapy and has evident medical importance. Here in this study, a PD-1 aptamer was functionalized with a tumor-homing nucleolin aptamer (AS1411) to build a novel bispecific agent (BiApt) for boosting the efficacy of ICB therapy. Results The two aptamers were coupled together via sticky ends to form BiApt, which had an average size of 11.70 nm. Flow cytometry revealed that BiApt could bind with both the activated T cells and the nucleolin-expressing tumor cells. In addition, BiApt could recruit more T cells to the vicinity of nucleolin-positive tumor cells. Functionally, BiApt enhanced the PBMC-mediated anticancer cytotoxicity in vitro compared with free PD-1 aptamer. Moreover, in an animal model of CT26 colon cancer, BiApt significantly boosted the antitumor efficacy vs. free PD-1 aptamer. Conclusion The results suggest that bispecific agent combining ICB and tumor-homing functions has potential to improve the efficacy of ICB immunotherapy.

show abstract

“…The application of extracellular immunomodulating aptamers has contributed to this therapeutic approach with several original concepts, as extensively reviewed by Thomas et al. ( 68 ). Due to the programmability of nucleic acids, aptamers can be rationally designed to assemble into higher order structures that enhance or even alter their original functionality.…”

Section: Aptamers As Extracellular Immunomodulatorsmentioning

confidence: 99%

“…The combinatorial potential of linking aptamers together offers not only the possibility of creating multivalent aptamers targeting the same or different epitopes of the same target molecule, but also the assembly of aptamers targeting diverse proteins. This presents an opportunity to promote specific cell-to-cell interactions, where the immune cell can anchor to the tumor cell and provide co-stimulatory signals more efficiently ( Figure 4B ) ( 68 – 71 ).…”

Section: Aptamers As Extracellular Immunomodulatorsmentioning

confidence: 99%

Therapeutic immunomodulation by rationally designed nucleic acids and nucleic acid nanoparticles

et al. 2023

View full text Add to dashboard Cite

The immune system has evolved to defend organisms against exogenous threats such as viruses, bacteria, fungi, and parasites by distinguishing between “self” and “non-self”. In addition, it guards us against other diseases, such as cancer, by detecting and responding to transformed and senescent cells. However, for survival and propagation, the altered cells and invading pathogens often employ a wide range of mechanisms to avoid, inhibit, or manipulate the immunorecognition. As such, the development of new modes of therapeutic intervention to augment protective and prevent harmful immune responses is desirable. Nucleic acids are biopolymers essential for all forms of life and, therefore, delineating the complex defensive mechanisms developed against non-self nucleic acids can offer an exciting avenue for future biomedicine. Nucleic acid technologies have already established numerous approaches in therapy and biotechnology; recently, rationally designed nucleic acids nanoparticles (NANPs) with regulated physiochemical properties and biological activities has expanded our repertoire of therapeutic options. When compared to conventional therapeutic nucleic acids (TNAs), NANP technologies can be rendered more beneficial for synchronized delivery of multiple TNAs with defined stabilities, immunological profiles, and therapeutic functions. This review highlights several recent advances and possible future directions of TNA and NANP technologies that are under development for controlled immunomodulation.

show abstract

Cancer immunomodulation using bispecific aptamers

Cited by 25 publications

References 177 publications

Targeting triple-negative breast cancer with β1-integrin binding aptamer

Targeting triple-negative breast cancer with β1-integrin binding aptamer

Novel Bispecific Aptamer Targeting PD-1 and Nucleolin for Cancer Immunotherapy

Therapeutic immunomodulation by rationally designed nucleic acids and nucleic acid nanoparticles

Contact Info

Product

Resources

About