Antibody nanoparticle conjugate-based targeted immunotherapy for non-small cell lung cancer

被引：12

作者：

Saha, Tanmoy ^{[1
,2
]}

Fojtu, Michaela ^{[1
,2
]}

Nagar, Astha Vinay ^{[1
,2
]}

Thurakkal, Liya ^{[1
,2
]}

Srinivasan, Balaaji Baanupriya ^{[1
,2
]}

Mukherjee, Meghma ^{[1
,2
]}

Sibiyon, Astralina ^{[1
,2
]}

Aggarwal, Heena ^{[1
,2
]}

Samuel, Akash ^{[1
,2
]}

Dash, Chinmayee ^{[1
,2
]}

Jang, Hae Lin ^{[2
,3
,4
]}

Sengupta, Shiladitya ^{[1
,2
,5
,6
]}

机构：

[1] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Engn Med, Boston, MA 02115 USA

[2] Harvard Med Sch, Brigham & Womens Hosp, Ctr Engn Therapeut, Dept Med, Boston, MA 02115 USA

[3] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Rheumatol Inflammat & Immun, Boston, MA USA

[4] Harvard Med Sch, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA USA

[5] Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA

[6] Dana Farber Canc Inst, Boston, MA 02215 USA

来源：

SCIENCE ADVANCES | 2024年 / 10卷 / 24期

关键词：

CD47; RESISTANCE; PD-L1; PEMBROLIZUMAB; CHEMOTHERAPY; EXPRESSION; BLOCKADE; EFFICACY; PATHWAY;

D O I：

10.1126/sciadv.adi2046

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The use of immune checkpoint inhibitors, which activate T cells, is a paradigm shift in the treatment of non-small cell lung cancer. However, the overall response remains low. To address this limitation, here we describe a novel platform, termed antibody-conjugated drug-loaded nanotherapeutics (ADN), which combines immunotherapy and molecularly targeted therapy. An ADN was designed with an anti-CD47 and anti-programmed death ligand 1 (PDL1) antibody pair on the surface of the nanoparticle and a molecularly targeted inhibitor of the PI3K (phosphatidylinositol 3-kinase)/AKT/mTOR (mammalian target of rapamycin) pathway, PI103, entrapped in the nanoparticle. The anti-CD47-PDL1-ADN exhibited greater antitumor efficacy than current treatment options with a PDL1 inhibitor in vivo in an aggressive lung cancer immunocompetent mouse model. Dual antibody-drug-loaded nanotherapeutics can emerge as an attractive platform to improve outcomes with cancer immunotherapy.

引用

页数：15

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