Redirecting natural killer cells to potentiate adoptive immunotherapy in solid tumors through stabilized Y-type bispecific aptamer

Abstract

In vivo modulating interactions between immune effector cells and tumor cells by bi-specific aptamer (Ap) is a promising strategy for cancer immunotherapy recently. However, it remains a technical challenge due...

Aptamer-functionalized nanomaterials (AFNs) for therapeutic management of hepatocellular carcinoma

“…Such targeted delivery not only optimizes drug concentration at the tumor site for minimal non-target impact but also modulates immune checkpoint activity, invigorating the immune response against tumor cells. A pivotal advantage of merging AFNs with immunotherapy lies in AFNs' capacity to concurrently transport various immunomodulators to the tumor milieu [ 114 ], enhancing immunotherapeutic outcomes. This dual action—direct targeting by AFNs and immune system engagement—potentiates immunotherapy's effectiveness against HCC, mitigating associated side effects and heralding innovative treatment avenues.…”

“…A recent development shows bispecific aptamers (Ap) have the potential to modulate interactions between immune effector cells and tumor cells, marking them as promising therapeutic agents to specifically enhance cancer immunotherapy. Zheng et al designed a stable, Y-shaped, bispecific Ap using a Y-shaped DNA scaffold to augment adoptive immunotherapy for HCC solid tumors [ 114 ]. This Y-type Ap, connecting HCC-specific Ap TLS11a with CD16-specific Ap through a Y-shaped DNA scaffold, is rigid, maintains considerable stability in 10% serum over 72 h, and resists the denaturing effect of 8 M urea.…”

Immunomodulation with Nucleic Acid Nanodevices

“…By nucleic acid hybridization, two specific aptamers linked by rigid dsDNA or dsRNA linker were assembled to form dsApt 1+1 nanodevice with better stability such as the reported anti-CD4/epithelial cell adhesion molecules (EpCAM) dsApt nanodevice and Y-shape DNA nanodevice targeting CD16 in NK cell and TSL11a in hepatocellular carcinoma (Figure 8B). [103] Compared with the hybridized dsApt nanodevice, circularized dsApt nanodevice by T4 DNA ligase-mediated covalent conjugation of the 5′-terminus and 3′-terminus dsApt exhibits superior nuclease resistance, while retaining its targeting affinity (Figure 8B). [104] Based on this methodology, a circular bsApt nanodevice was developed to bridge T cells and tumor cells to form junctional cell-cell complexes (Figure 8C).…”

Cancer immunomodulation using bispecific aptamers

“… 75 Hepatocellular carcinoma ( TSL11a ) [DNA] CD16 ( CLN0020 a ) [DNA] NK cell activation Rigid Y-type DNA scaffold Zheng et al. 76 , b 1 + 2 VEGF ( ARC245 ) [DNA] 4-1BB ( M12-23 ) [2′FY RNA] Co-stimulation 24-nt adapter (complementary) sequence extended on 3′ end of each aptamer Schrand et al. 77 OPN ( OPN-R3 ) [DNA] 4-1BB ( M12-23 ) [2′FY RNA] Co-stimulation 24-nt adapter (complementary) sequence extended on 3′ end of each aptamer Schrand et al.…”