Aptamer-Based Strategies to Boost Immunotherapy in TNBC

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.

Bispecific aptamer-decorated and light-triggered nanoparticles targeting tumor and stromal cells in breast cancer derived organoids: implications for precision phototherapies

“…To this aim we have employed oligonucleotide aptamers as cell targeting agents because of their stability, ease of manufacture at high reproducibility, and low or absent immunogenicity. Their chemical synthesis and versatility for chemical modification allow easier conjugation to different kinds of nanoplatforms, at higher yield and lower costs, than other form of ligands as antibodies or peptides [ 28 , 64 ], which is relevant for industrial scale up. To date, a limited number of dual-aptamer modified nanoplatforms have been developed for achieving cancer therapeutic efficacy superior to that of single targeting through the recognition of different tumor cell types [ 65 , 66 ] or different receptors on the same tumor cells [ 67 , 68 ] and, to the best of our knowledge, this is the first study exploring bispecific nanoparticles with two different aptamers for exerting excellent anti-tumor cytotoxic effects on both tumor cells and the reactive stroma.…”

Tissue Inhibitor of Metalloproteinases-1 Overexpression Mediates Chemoresistance in Triple-Negative Breast Cancer Cells

“…TNBC is a highly heterogeneous tumor comprising subtypes that differ not only in histopathology and gene expression, but also in prognosis and response to therapies [ 41 , 59 ]. Because of the lack of actionable biomarkers for managing each specific subtype, therapy for TNBC still remains inadequate, with only four targeted therapies (PARP inhibitors, immunomodulatory Atezolizumab and Pembrolizumab monoclonal antibodies, and Sacituzumab Govitecan antibody–drug conjugate) applicable to a restrict number of TNBC patients and always in combination with a chemotherapeutic regimen [ 60 ]. Thus, most patients with TNBC are still treated exclusively with chemotherapy.…”

Aptamer-based Theranostics in Oncology: Design Strategies and Limitations

“…Moreover, aptamers can be engineered to overcome acquired resistance by targeting alternative pathways or biomarkers that are still present in resistant cancer cells. Furthermore, combining aptamer-based theranostics with other treatment modalities, such as chemotherapy or immunotherapy, can enhance the overall efficacy of cancer therapy [5].…”