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Updated: Jun 23, 2025
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Antibody nanoparticle conjugate-based targeted immunotherapy for non-small cell lung cancer
Tanmoy Saha1,2, Michaela Fojtů1,2, Astha Vinay Nagar1,2
1Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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.
Insights
A novel antibody-conjugated drug-loaded nanotherapeutic (ADN) platform combines immunotherapy and targeted therapy for non-small cell lung cancer. This dual approach shows improved antitumor efficacy compared to current treatments in preclinical models.
Area of Science:
- Oncology
- Immunotherapy
- Nanomedicine
- Drug Delivery
Background:
- Immune checkpoint inhibitors represent a significant advancement in non-small cell lung cancer (NSCLC) treatment by activating T cells.
- Despite advancements, the overall response rates for current immunotherapies in NSCLC remain suboptimal.
- Combining immunotherapy with molecularly targeted therapy offers a potential strategy to overcome treatment resistance.
Purpose of the Study:
- To develop and evaluate a novel antibody-conjugated drug-loaded nanotherapeutic (ADN) platform.
- To investigate the potential of combining anti-CD47 and anti-programmed death ligand 1 (PDL1) immunotherapy with PI3K/AKT/mTOR pathway inhibition via ADN.
- To assess the antitumor efficacy of the developed ADN compared to existing therapies in a preclinical lung cancer model.
Main Methods:
- Design of an ADN platform featuring an anti-CD47 and anti-PDL1 antibody pair on the nanoparticle surface.
- Encapsulation of PI103, a molecularly targeted inhibitor of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, within the nanoparticle.
- In vivo evaluation of the anti-CD47-PDL1-ADN's antitumor efficacy in an aggressive lung cancer immunocompetent mouse model.
Main Results:
- The developed anti-CD47-PDL1-ADN demonstrated superior antitumor efficacy compared to treatment with a PDL1 inhibitor alone.
- The combination strategy within the ADN platform showed enhanced therapeutic effects in a challenging preclinical lung cancer model.
- The study validates the potential of dual-targeting nanotherapeutics in overcoming limitations of current cancer immunotherapies.
Conclusions:
- Antibody-conjugated drug-loaded nanotherapeutics (ADN) represent a promising platform for integrating immunotherapy and molecularly targeted therapy.
- Dual antibody targeting combined with targeted drug delivery via ADN can significantly enhance antitumor responses.
- This innovative nanotherapeutic approach holds potential for improving patient outcomes in non-small cell lung cancer and other malignancies.
