Leveraging Senescent Cancer Cell Membrane to Potentiate Cancer Immunotherapy Through Biomimetic Nanovaccine.
Chao YangYinglu ChenJie LiuWensheng ZhangYan HeFangman ChenXiaochun XieJie TangShan GuanDan ShaoZheng WangLiang WangPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cancer cell-based vaccination is limited by interference from immunosuppressive senescence-associated secretory phenotype and pro-tumorigenic capacity of senescent cells. Here, a senescent cancer cell-based nanovaccine with strong immunogenicity and favorable potential for immunotherapy is reported. The biomimetic nanovaccine integrating a senescent cancer cell membrane-coated nanoadjuvant outperforms living senescent cancer cells in enhancing dendritic cells (DCs) internalization, improving lymph node targeting, and enhancing immune responses. In contrast to nanovaccines generated from immunogenic cell death-induced tumor cells, senescent nanovaccines facilitate DC maturation, eliciting superior antitumor protection and improving therapeutic outcomes in melanoma-challenged mice with fewer side effects when combined with αPD-1. The study suggests a versatile biomanufacturing approach to maximize immunogenic potential and minimize adverse effects of senescent cancer cell-based vaccination and advances the design of biomimetic nanovaccines for cancer immunotherapy.
Keyphrases
- dendritic cells
- lymph node
- immune response
- cell death
- papillary thyroid
- type diabetes
- cell cycle arrest
- magnetic resonance
- induced apoptosis
- squamous cell
- young adults
- toll like receptor
- skeletal muscle
- adipose tissue
- dna damage
- cell proliferation
- early stage
- computed tomography
- radiation therapy
- metabolic syndrome
- insulin resistance
- climate change
- high glucose
- oxidative stress
- endothelial cells
- diabetic rats
- weight loss