%0 Journal Article
%T Antibody nanoparticle conjugate-based targeted immunotherapy for non-small cell lung cancer.
%A Saha T
%A Fojtů M
%A Nagar AV
%A Thurakkal L
%A Srinivasan BB
%A Mukherjee M
%A Sibiyon A
%A Aggarwal H
%A Samuel A
%A Dash C
%A Jang HL
%A Sengupta S
%J Sci Adv
%V 10
%N 24
%D 2024 Jun 14
%M 38875335
%F 14.957
%R 10.1126/sciadv.adi2046
%X 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.