Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy.
Yuanzeng MinKyle C RocheShaomin TianMichael J EblanKaren P McKinnonJoseph M CasterShengjie ChaiLaura E HerringLongzhen ZhangTian ZhangJoseph M DeSimoneJoel E TepperBenjamin G VincentJonathan S SerodyAndrew Z WangPublished in: Nature nanotechnology (2017)
Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties. We showed that AC-NPs deliver tumour-specific proteins to antigen-presenting cells (APCs) and significantly improve the efficacy of αPD-1 (anti-programmed cell death 1) treatment using the B16F10 melanoma model, generating up to a 20% cure rate compared with 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4+T/Treg and CD8+T/Treg ratios (Treg, regulatory T cells). Our work presents a novel strategy to improve cancer immunotherapy with nanotechnology.
Keyphrases
- regulatory t cells
- dendritic cells
- immune response
- induced apoptosis
- early stage
- oxide nanoparticles
- case report
- drug delivery
- radiation therapy
- oxidative stress
- high glucose
- toll like receptor
- cell cycle arrest
- endoplasmic reticulum stress
- case control
- binding protein
- cell death
- drug induced
- big data
- artificial intelligence
- endothelial cells
- radiation induced