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

Autor: Saha T; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Fojtů M; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Nagar AV; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Thurakkal L; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Srinivasan BB; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Mukherjee M; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Sibiyon A; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Aggarwal H; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Samuel A; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Dash C; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Jang HL; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Sengupta S; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA, USA.; Dana-Farber Cancer Institute, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 Jun 14; Vol. 10 (24), pp. eadi2046. Date of Electronic Publication: 2024 Jun 14.
DOI: 10.1126/sciadv.adi2046
Abstrakt: 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.
Databáze: MEDLINE