Chemotherapy-Induced Neoantigen Nanovaccines Enhance Checkpoint Blockade Cancer Immunotherapy.
Guiyuan ChenXiangxia LiRui LiKecheng WuZhouhang LeiRuike DaiKyle RocheAndrew Z WangYuanzeng MinPublished in: ACS nano (2023)
Chemotherapeutics have the potential to increase the efficacy of cancer immunotherapies by stimulating the production of damage-associated molecular patterns (DAMPs) and eliciting mutations that result in the production of neoantigens, thereby increasing the immunogenicity of cancerous lesions. However, the dose-limiting toxicity and limited immunogenicity of chemotherapeutics are not sufficient to induce a robust antitumor response. We hypothesized that cancer cells in vitro treated with ultrahigh doses of various chemotherapeutics artificially increased the abundance, variety, and specificity of DAMPs and neoantigens, thereby improving chemoimmunotherapy. The in vitro chemotherapy-induced (IVCI) nanovaccines manufactured from cell lysates comprised multiple neoantigens and DAMPs, thereby exhibiting comprehensive antigenicity and adjuvanticity. Our IVCI nanovaccines exhibited enhanced immune responses in CT26 tumor-bearing mice, with a significant increase in CD4 + /CD8 + T cells in tumors in combination with immune checkpoint inhibitors. The concept of IVCI nanovaccines provides an idea for manufacturing and artificial enhancement of immunogenicity vaccines to improve chemoimmunotherapy.
Keyphrases
- chemotherapy induced
- immune response
- oxidative stress
- papillary thyroid
- dna damage
- computed tomography
- single cell
- cell cycle
- high fat diet induced
- squamous cell
- cell therapy
- image quality
- contrast enhanced
- magnetic resonance imaging
- risk assessment
- magnetic resonance
- mesenchymal stem cells
- antibiotic resistance genes
- metabolic syndrome
- dendritic cells
- lymph node metastasis
- single molecule
- bone marrow
- wild type