Fluorobenzylation promotes immune-activating peptides to turn cold tumors into hot tumors
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Fluorobenzylation enhances peptide immunogenicity, converting "cold" tumors into "hot" ones. This novel nanoparticle platform effectively delivers the peptide, boosting immunotherapy responses against cancer.
Area Of Science
- Oncology
- Immunology
- Nanotechnology
- Drug Delivery
Background
- Immunologically
- cold
- tumors are resistant to immunotherapy.
- Novel strategies are needed to enhance immunogenicity and T-cell infiltration.
- Peptide modifications can improve stability and membrane interactions.
Purpose Of The Study
- To develop a sequence-dependent peptide modification, fluorobenzylation, to enhance immunogenicity.
- To create nanoparticle-based delivery systems for enhanced tumor penetration and intracellular release.
- To evaluate the efficacy of fluorobenzylated peptide nanoparticles (FPNPs) in converting cold tumors and potentiating immunotherapy.
Main Methods
- Synthesis and characterization of fluorobenzylated peptides (FPP5).
- Assembly of FPP5 into composition-defined nanoparticles (FPNPs) with controlled size and stability.
- In vitro assessment of immunogenic cell death (ICD) hallmarks and spheroid penetration.
- In vivo evaluation in a breast cancer model using PET tracking and combination therapy with anti-PD-L1.
Main Results
- Fluorobenzylation significantly increased peptide immunogenicity and ICD hallmarks compared to native peptides.
- FPNPs demonstrated serum stability, low critical aggregation concentration (CAC), and efficient intracellular release of bioactive FPP5.
- FPNPs enhanced tumor penetration and accumulation, potentiated ICD, increased CD8+ T-cell infiltration, and synergized with anti-PD-L1 therapy.
Conclusions
- Fluorobenzylation is a potent sequence-dependent method to amplify peptide immunogenicity.
- FPNPs provide a programmable platform for efficient delivery, intracellular release, and conversion of cold tumors to hot lesions.
- This approach holds promise for enhancing cancer immunotherapy, particularly in combination regimens.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...