What is it about?
We report here a new liposomal nanoparticle (NP) loaded with cyclic dinucleotide (CDN), a potent immunostimulant. Unlike the conventional cancer drug delivery, we develop a nebulizer system to aerosolize the NPs for inhalation delivery to deep-seated lung tumors. The inhaled NPs are deposited into individual lung tumors and taken up by one specific type of immune cells, called antigen-presenting cells (APCs). CDN in the nanoparticle is then released inside the cell, where a particular immune pathway (STING) is activated in APCs, which is a critical step to induce systemic anti-cancer immune responses. We investigated its therapeutic effect in a mouse model of advanced lung cancer by combining with the immune checkpoint inhibitor, anti-PD-L1 antibody. The combination immunotherapy was hugely promising; there was regression of both lung tumors, prolonged survival, and even complete removal of the tumor in several mice.
Featured Image
Why is it important?
Despite therapeutic advancements, prognosis of lung cancer remains poor. In particular, locally advanced lung cancer, which has spread to lymph nodes and other lobes or the opposite lung has a five-year survival rate <5%. The emergence of immunotherapy with immune checkpoint blockade (ICB) is providing tremendous promise in cancer treatment. However, only a fraction of non-small cell lung cancer (NSCLC) patients (<20%) benefit from ICB. Thus, development of new therapeutics to improve NSCLC immunotherapy is urgently needed. We show in this study that the newly developed nanoparticle immunotherapeutic delivered via inhalation successfully enhances the immune checkpoint blockade therapy against advanced lung cancer in a mouse model.
Perspectives
Previous approaches have involved direct injection of immunomodulators into tumors to boost their immune response. However, this approach is generally limited to surface and easily-accessed tumors, and can become less effective if repeated injections are needed to sustain immune response. The newly designed nanoparticle therapy is therefore attractive over previous approaches as it is delivered by inhalation. The nanoparticle-immunotherapy was additionally well-tolerated by the mice, able to reach all areas of the lung, and has great potential as a repeating treatment. This method could be used in the future to access deep-seated lung tumors that are unreachable by the current injection immunotherapy techniques.
Dawen Zhao
Wake Forest University School of Medicine
Read the Original
This page is a summary of: Aerosolized immunotherapeutic nanoparticle inhalation potentiates PD-L1 blockade for locally advanced lung cancer, Nano Research, December 2022, Tsinghua University Press,
DOI: 10.1007/s12274-022-5205-6.
You can read the full text:
Contributors
The following have contributed to this page
