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

被引：8

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

共 50 条

[1] Targeted immunotherapy for non-small cell lung cancer
Vasekar, Monali
Liu, Xin
Zheng, Hong
Belani, Chandra P.
WORLD JOURNAL OF CLINICAL ONCOLOGY, 2014, 5 (02): : 39 - 47
[2] Immunotherapy as a targeted therapy in non-small cell lung cancer
Rocco, Danilo
Della Gravara, Luigi
Avellino, Aniello
Montesarchio, Vincenzo
Battiloro, Ciro
TRANSLATIONAL CANCER RESEARCH, 2019, 8 : S70 - S75
[3] Targeted Therapy and Immunotherapy in the Treatment of Non-Small Cell Lung Cancer
Shroff, Girish S.
de Groot, Patricia M.
Papadimitrakopoulou, Vassiliki A.
Truong, Mylene T.
Carter, Brett W.
RADIOLOGIC CLINICS OF NORTH AMERICA, 2018, 56 (03) : 485 - +
[4] Immunotherapy for Non-Small Cell Lung Cancer
Yoon, Sung Ho
TUBERCULOSIS AND RESPIRATORY DISEASES, 2014, 77 (03) : 111 - 115
[5] Immunotherapy for non-small cell lung cancer
Vafadar, Sam
JAAPA-JOURNAL OF THE AMERICAN ACADEMY OF PHYSICIAN ASSISTANTS, 2019, 32 (09): : 37 - 42
[6] Immunotherapy in non-small cell lung cancer
Peters, Geoffrey
John, Thomas
CANCER FORUM, 2018, 42 (01) : 24 - 28
[7] Immunotherapy in the landscape of new targeted treatments for non-small cell lung cancer
Gerard, Catherine
Debruyne, Channa
MOLECULAR ONCOLOGY, 2009, 3 (5-6) : 409 - 424
[8] Immunotherapy for non-small cell lung cancer
Kagamu, Hiroshi
RESPIRATORY INVESTIGATION, 2024, 62 (02) : 307 - 312
[9] Advances in Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer Based on Accurate Molecular Typing
Dong, Jingsi
Li, Bingjie
Lin, Dan
Zhou, Qinghua
Huang, Depei
FRONTIERS IN PHARMACOLOGY, 2019, 10
[10] Combination of immunotherapy with targeted therapies in advanced non-small cell lung cancer (NSCLC)
Moya-Horno, Irene
Viteri, Santiago
Karachaliou, Niki
Rosell, Rafael
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, 2018, 10

← 1 2 3 4 5 →