Blockading a new NSCLC immunosuppressive target by pluripotent autologous tumor vaccines magnifies sequential immunotherapy.
Blockading a new NSCLC immunosuppressive target by pluripotent autologous tumor vaccines magnifies sequential immunotherapy.
复制标题
通过多能自体肿瘤疫苗阻断新的 NSCLC 免疫抑制靶点可放大序贯免疫治疗
DOI：
10.1016/j.bioactmat.2021.10.048
复制
发表时间：
2022-07
影响因子：
18.9
通讯作者：
Xu C
中科院分区：
文献类型：
--
作者：
Wu H;Li H;Liu Y;Liang J;Liu Q;Xu Z;Chen Z;Zhang X;Zhang K;Xu C
存在多种免疫抑制靶标，细胞毒性T淋巴细胞（CTL）的激活和浸润不足，肿瘤细胞可以逃脱免疫监测并使抗PD-1/PD-1/PD-L1免疫疗法失败。纳米生物技术工程工程的自体肿瘤疫苗（ATV）设计为肿瘤细胞膜（TCM）伪装，以激活和促进CTLS浸润以杀死未受保护的肺肿瘤细胞，从而杀死顺序免疫疗法。在临床实践中，PDE5首先被筛选为肺癌的新免疫抑制靶标。此后，提出了磷酸二酯酶5（PDE5）和程序性细胞死亡1配体1（PD-L1）双目标共抑制作用，以结束NSCLC的免疫抑制微环境。 Systematic studies validated that this ATVs-unlocked sequential immunotherapy after co-encapsulating PDE5 inhibitor and NO donor (i.e., l-arginine) exerted robust anti-tumor effects through increasing inducible nitric oxide synthase (iNOS) expression, blockading PDE5 pathway and activating systematic immune responses, which synergistically eradicated local and abscopal lung在原位或皮下模型中的癌症。能够抑制PDE5和顺序免疫疗法的多能ATV为减轻免疫抑制的微环境提供了新的途径，并放大了抗PD-1/PD-L1免疫疗法。
PDE5已被筛选为一种新的NSFC免疫抑制靶标，基于纳米生物学技术工程的自体肿瘤疫苗（ATV）旨在激活和促进CTLS浸润，以杀死未经保护的肺部或较高的肺部抗lung肿瘤，并在局部抗lung肿瘤中，或者实现了对局部免疫疗法的侵害，或在抑制PDE5和PD-L1双目标之后，尤其是在没有供体（即L-精氨酸）时，模型。
实验验证了用于设计新药物的临床筛查的NSCLC免疫抑制靶标（PDE5）。
多能ATV通过PDE5和PD-L1共抑制和TCM抗原芳香的免疫激活解锁顺序免疫疗法。
在ATV中，没有加载的供体增强PDE5I的功效，并放大了依赖TCM的肿瘤疗法的顺序免疫疗法。
The presence of multiple immunosuppressive targets and insufficient activation and infiltration of cytotoxic T lymphocytes (CTLs) allow tumor cells to escape immune surveillance and disable anti-PD-1/PD-L1 immunotherapy. Nanobiotechnology-engineered autologous tumor vaccines (ATVs) that were camouflaged by tumor cell membrane (TCM) were designed to activate and facilitate CTLs infiltration for killing the unprotected lung tumor cells, consequently realizing the sequential immunotherapy. PDE5 was firstly screened out as a new immunosuppressive target of lung cancer in clinical practice. Immediately afterwards, phosphodiesterase-5 (PDE5) and programmed cell death 1 ligand 1 (PD-L1) dual-target co-inhibition was proposed to unfreeze the immunosuppressive microenvironment of NSCLC. Systematic studies validated that this ATVs-unlocked sequential immunotherapy after co-encapsulating PDE5 inhibitor and NO donor (i.e., l-arginine) exerted robust anti-tumor effects through increasing inducible nitric oxide synthase (iNOS) expression, blockading PDE5 pathway and activating systematic immune responses, which synergistically eradicated local and abscopal lung cancers in either orthotopic or subcutaneous models. The pluripotent ATVs that enable PDE5 inhibition and sequential immunotherapy provide a new avenue to mitigate immunosuppressive microenvironment and magnify anti-PD-1/PD-L1 immunotherapy. PDE5 has been screened out as a new NSFC immunosuppressive target, based on which nanobiotechnology-engineered autologous tumor vaccines (ATVs) were designed to activate and facilitate CTLs infiltration for killing the unprotected lung tumor cells, consequently realizing the sequential immunotherapy against local and abscopal lung cancers in either orthotopic or subcutaneous models after inhibiting PDE5 and PD-L1 dual-targets, expecially upon to uniting NO donor (i.e., l-arginine). A clinically-screened NSCLC immunosuppressive target (PDE5) is experimentally validated available for designing new drugs. Pluripotent ATVs unlock sequential immunotherapy via PDE5&PD-L1 co-inhibition and TCM antigens-arised immune activation. NO donor loaded in ATVs augmented PDE5i efficacy and magnified sequential immunotherapy along with TCM-enabled tumor tropism.
登录
查看更多内容
影响因子：
64.8
作者：
Manguso RT;Pope HW;Zimmer MD;Brown FD;Yates KB;Miller BC;Collins NB;Bi K;LaFleur MW;Juneja VR;Weiss SA;Lo J;Fisher DE;Miao D;Van Allen E;Root DE;Sharpe AH;Doench JG;Haining WN
通讯作者：
Haining WN
影响因子：
3
作者：
Dunkerly-Eyring B;Kass DA
通讯作者：
Kass DA
影响因子：
11.4
作者：
Cortese-Krott MM;Mergia E;Kramer CM;Lückstädt W;Yang J;Wolff G;Panknin C;Bracht T;Sitek B;Pernow J;Stasch JP;Feelisch M;Koesling D;Kelm M
通讯作者：
Kelm M
影响因子：
11.4
作者：
Cheriyan, Vino T.;Alfaidi, Mabruka;Nam, Hyung W.
通讯作者：
Nam, Hyung W.
影响因子：
64.5
作者：
Devalaraja, Samir;To, Tsun Ki Jerrick;Haldar, Malay
通讯作者：
Haldar, Malay