Antibody nanoparticle conjugate–based targeted immunotherapy for non–small cell lung cancer
Tanmoy Saha, Michaela Fojtů, Astha Vinay Nagar, Liya Thurakkal, Balaaji Baanupriya Srinivasan, M. Mukherjee, Astralina Sibiyon, Heena Aggarwal, Akash Samuel, Chinmayee Dash, Hae Lin Jang, Shiladitya Sengupta
Abstract
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.