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

• DOI: 10.1126/sciadv.adi2046
• Publication Date: 2024-06-14T17:58:18Z
• Authors: Tanmoy Saha; Michaela Fojtů; Astha Vinay Nagar; Liya Thurakkal; Balaaji Baanupriy...; Meghma Mukherjee; Astralina Sibiyon; Heena Aggarwal; Akash Samuel; Chinmayee Dash; Hae Lin Jang; Shiladitya Sengupta
• Keywords: 0303 health sciences; Lung Neoplasms; Immunoconjugates; CD47 Antigen; Xenograft Model Antitumor Assays; B7-H1 Antigen; Mice; Disease Models, Animal; 03 medical and health sciences; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Animals; Humans; Nanoparticles; Biomedicine and Life Sciences; Immunotherapy; Immune Checkpoint Inhibitors

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.