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RESEARCH PRODUCT
Novel Opportunities for Cathepsin S Inhibitors in Cancer Immunotherapy by Nanocarrier-Mediated Delivery
Natalie FuchsLutz NuhnMergim MetaDetlef SchuppanDetlef SchuppanTanja Schirmeistersubject
0301 basic medicineT-Lymphocytesmedicine.medical_treatmentReview02 engineering and technologyCancer immunotherapyNeoplasmsTumor-Associated MacrophagesTumor Microenvironmentcysteine proteaseMolecular Targeted TherapySulfoneslcsh:QH301-705.5Cathepsin SAntigen PresentationDrug Carrierscysteine cathepsintumor-associated macrophage (TAM)ChemistrynanoparticleAzepinesDipeptidesGeneral Medicine021001 nanoscience & nanotechnologyGene Expression Regulation NeoplasticImmunotherapy0210 nano-technologydendritic cellAntigen presentationAntineoplastic AgentsTumor-associated macrophageM2 macrophage03 medical and health sciencesLeucinemedicineHumansProtease InhibitorsAntigen-presenting celltargetingtherapypolarizationTumor microenvironmentT cellDendritic CellsDendritic cellextracellular matrix (ECM)Cathepsinstumor associated macrophage030104 developmental biologylcsh:Biology (General)antigen presenting cellCancer researchNanoparticlesimmune suppressionNanocarriersdescription
Cathepsin S (CatS) is a secreted cysteine protease that cleaves certain extracellular matrix proteins, regulates antigen presentation in antigen-presenting cells (APC), and promotes M2-type macrophage and dendritic cell polarization. CatS is overexpressed in many solid cancers, and overall, it appears to promote an immune-suppressive and tumor-promoting microenvironment. While most data suggest that CatS inhibition or knockdown promotes anti-cancer immunity, cell-specific inhibition, especially in myeloid cells, appears to be important for therapeutic efficacy. This makes the design of CatS selective inhibitors and their targeting to tumor-associated M2-type macrophages (TAM) and DC an attractive therapeutic strategy compared to the use of non-selective immunosuppressive compounds or untargeted approaches. The selective inhibition of CatS can be achieved through optimized small molecule inhibitors that show good pharmacokinetic profiles and are orally bioavailable. The targeting of these inhibitors to TAM is now more feasible using nanocarriers that are functionalized for a directed delivery. This review discusses the role of CatS in the immunological tumor microenvironment and upcoming possibilities for a nanocarrier-mediated delivery of potent and selective CatS inhibitors to TAM and related APC to promote anti-tumor immunity.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-09-02 |