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Review
. 2023 Mar 28;15(7):2010.
doi: 10.3390/cancers15072010.

Aptamer-Based Strategies to Boost Immunotherapy in TNBC

Lisa Agnello  1 , Annachiara d'Argenio  1 , Roberto Nilo  1 , Monica Fedele  1 , Simona Camorani  1 , Laura Cerchia  1
Affiliations
Review

Aptamer-Based Strategies to Boost Immunotherapy in TNBC

Lisa Agnello et al. Cancers (Basel). .

Abstract

The immune system (IS) may play a crucial role in preventing tumor development and progression, leading, over the last years, to the development of effective cancer immunotherapies. Nevertheless, immune evasion, the capability of tumors to circumvent destructive host immunity, remains one of the main obstacles to overcome for maximizing treatment success. In this context, promising strategies aimed at reshaping the tumor immune microenvironment and promoting antitumor immunity are rapidly emerging. Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor outcomes, is highly immunogenic, suggesting immunotherapy is a viable strategy. As evidence of this, already, two immunotherapies have recently become the standard of care for patients with PD-L1 expressing tumors, which, however, represent a low percentage of patients, making more active immunotherapeutic approaches necessary. Aptamers are short, highly structured, single-stranded oligonucleotides that bind to their protein targets at high affinity and specificity. They are used for therapeutic purposes in the same way as monoclonal antibodies; thus, various aptamer-based strategies are being actively explored to stimulate the IS's response against cancer cells. The aim of this review is to discuss the potential of the recently reported aptamer-based approaches to boost the IS to fight TNBC.

Keywords: TNBC; active cancer targeting; aptamer; immune system; immunotherapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of aptamer binding to its target and key steps of the SELEX method. (a) The aptamer adopts a 3D structure to bind to its target; (b) The SELEX starts with random libraries of ssDNA or RNA sequences and comprises reiterated rounds of binding to the target, partitioning of the target bound sequences from unbound and amplification of the bound sequences. Finally, the enriched library is analyzed by cloning and sequencing or, in the most recent approaches, high-affinity ligands are identified by next-generation sequencing (NGS) and bioinformatics. Created with BioRender.com (accessed on 2 March 2023).
Figure 2
Figure 2
Aptamer-based anticancer therapy. (a) Antagonistic therapy: aptamers bind to cancer cell surface targets, inhibiting protumoral pathways. (b) Targeted drug delivery: aptamers conjugated to drug-loaded nanoparticles or linked to drugs bind to cell surface targets and internalize into cancer cells, resulting in selective intracellular drug delivery. (c) Gene therapy: aptamers decorating small-interfering RNA (siRNA)-loaded nanoparticles or conjugated directly to siRNA, bind to cell surface targets and internalize into cancer cells, resulting in selective gene silencing. (d) Immunotherapy: aptamers stimulate immune cells against cancer cells (see text for details). Created with BioRender.com (accessed on 2 March 2023).
Figure 3
Figure 3
Schematic representation of the most common strategies for chemically modifying aptamers in order to improve their clinical applicability. Created with BioRender.com (accessed on 2 March 2023).
Figure 4
Figure 4
Aptamer-based strategies to restore an antitumoral immune TME. In TNBC, aptamers have been used for: (a) potentiating the cytotoxic activity of CD8+ T cells; (b) blocking immune checkpoint proteins from binding with their partners; and (c) restoring antitumoral TME through the recruitment of aptamer-engineered immune cells (macrophages and NK cells) to the tumor (see text for details). Created with BioRender.com (accessed on 2 March 2023).
Figure 5
Figure 5
Schematic representation of aptamer-based strategies to block PD-1/PD-L1 axis in TNBC. (a) TNBC aptamer-decorated nanoparticles loaded with anti-PD-L1 siRNA; (b) anti-CD44 and anti-PD-L1 aptamer-decorated liposomes loaded with both doxorubicin and anti-IDO1 siRNA; (c) anti-PD-L1 aptamer conjugated to paclitaxel; (d) anti-EGFR aptamer covalently linked to anti-PD-L1 or anti-CTLA-4 mAbs (see text for details). Created with BioRender.com (accessed on 2 March 2023).
Figure 6
Figure 6
Schematic representation of PSA macrophage engineering strategy (see text for details). Created with BioRender.com (accessed on 2 March 2023).
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