Cell Surface‐Tethered Nucleic Acid Therapeutics Program Robust and Tumor‐Responsive Enhancement of Adoptive Cell Therapy DOI
Mengqian Gao, Yingyu Liu, Lei Zhao

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Abstract The efficacy of adoptive T cell therapy (ACT) against solid tumors is significantly limited by the immunosuppressive tumor microenvironment (TME). Systemic administration immunostimulants provides inadequate support to ACT cells and often elicits systemic toxicities. Here we present cell‐surface‐anchored nucleic acid therapeutics (NATs) robustly enhance through synergistic blockade adenosine PD‐1/PD‐L1 pathways in tumors. Two distinct NATs‐DNA aptamers targeting PD‐L1 (aptPD‐L1) ATP (aptATP)‐are engineered form partially‐hybridized duplexes (aptDual) that can efficiently anchor surface before transfer. Backpacked aptDual spatial‐temporally co‐localize with vivo jointly infiltrate ATP‐rich TME. Upon binding ATP, dissociates responsively release aptPD‐L1. Concurrently, aptATP scavenges extracellular its metabolite disrupt inhibitory adenosinergic axis, thereby sensitizing immune checkpoint This dual inhibition elicited a remarkable 40‐fold increase functional tumor‐infiltrating cells, substantially boosting TCR‐T CAR‐T multiple models, even immunologically “cold” NAT backpacks provide facile, versatile, safe strategy augment various ACTs

Language: Английский

Chimeric Antigen Receptor Cells Solid Tumor Immunotherapy Assisted by Biomaterials Tools DOI
Yujun Song, Yifan Wang,

Jianping Man

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Chimeric antigen receptor (CAR) immune cell therapies have revolutionized oncology, particularly in hematological malignancies, yet their efficacy against solid tumors remains limited due to challenges such as dense stromal barriers and immunosuppressive microenvironments. With advancements nanobiotechnology, researchers developed various strategies methods enhance the CAR tumor treatment. In this Review, we first outline structure mechanism of CAR-T (T, T cell), CAR-NK (NK, natural killer), CAR-M (M, macrophage) deeply analyze potential these cells treatment they face. Next, explore how biomaterials can optimize treatments by improving microenvironment, controlling release, promoting infiltration, enhancing efficacy. Finally, summarize current solutions, emphasize effective combination therapy, look forward its future clinical application strategies. This Review provides important theoretical perspectives practical guidance for development more

Language: Английский

Citations

0
Cell Surface‐Tethered Nucleic Acid Therapeutics Program Robust and Tumor‐Responsive Enhancement of Adoptive Cell Therapy DOI
Mengqian Gao, Yingyu Liu, Lei Zhao

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Abstract The efficacy of adoptive T cell therapy (ACT) against solid tumors is significantly limited by the immunosuppressive tumor microenvironment (TME). Systemic administration immunostimulants provides inadequate support to ACT cells and often elicits systemic toxicities. Here we present cell‐surface‐anchored nucleic acid therapeutics (NATs) robustly enhance through synergistic blockade adenosine PD‐1/PD‐L1 pathways in tumors. Two distinct NATs‐DNA aptamers targeting PD‐L1 (aptPD‐L1) ATP (aptATP)‐are engineered form partially‐hybridized duplexes (aptDual) that can efficiently anchor surface before transfer. Backpacked aptDual spatial‐temporally co‐localize with vivo jointly infiltrate ATP‐rich TME. Upon binding ATP, dissociates responsively release aptPD‐L1. Concurrently, aptATP scavenges extracellular its metabolite disrupt inhibitory adenosinergic axis, thereby sensitizing immune checkpoint This dual inhibition elicited a remarkable 40‐fold increase functional tumor‐infiltrating cells, substantially boosting TCR‐T CAR‐T multiple models, even immunologically “cold” NAT backpacks provide facile, versatile, safe strategy augment various ACTs

Language: Английский

Citations

0