A Dendrimer Peptide (KK2DP7) Delivery System with Dual Functions of Lymph Node Targeting and Immune Adjuvants as a General Strategy for Cancer Immunotherapy
Authors:
Open Access
- 22 March 2023
- journal article
- research article
- Published by Wiley in Advanced Science
- Vol. 10 (15)
Abstract
The clinical efficacy of personalized cancer vaccines still needs to be improved due to their insufficient immune effect. The development of innovative adjuvants and lymph node‐targeted delivery systems is the key to improving the clinical efficacy of personalized vaccines. However, there is still a lack of an adjuvant delivery system that is simple in preparation and capable of mass production and integrates adjuvant and lymph node targeted delivery functions. Here, this work reports that a simple dendrimer polypeptide (KK2DP7) nanoparticle enhances the immune efficacy of an OVA/neoantigen‐based vaccine. Due to its multiple functions as a delivery vehicle, immune adjuvant, and facilitator of dendritic cell migration, KK2DP7 efficiently increases the efficiency of antigen uptake and cross‐presentation by antigen‐presenting cells (APCs) and delivers antigens to lymph nodes via APCs. Strikingly, the antitumor effect of KK2DP7/OVA is superior to that of commonly used adjuvants such as poly(I:C), CpG, and aluminum adjuvant combined with OVA. Furthermore, KK2DP7/OVA combined with anti‐PD‐1 antibody is able to prevent tumor recurrence in a postoperative recurrent tumor model. Thus, KK2DP7‐based cancer vaccines alone or in combination with immune checkpoint blockade therapies to treat tumors or postoperative tumor recurrence are a powerful strategy to enhance antitumor immunity.Keywords
Funding Information
- National Natural Science Foundation of China (32100748, 82073366)
This publication has 35 references indexed in Scilit:
- Nano-chemotherapeutics: Maximising lymphatic drug exposure to improve the treatment of lymph-metastatic cancersJournal of Controlled Release, 2014
- In Vitro and In Vivo Activities of Antimicrobial Peptides Developed Using an Amino Acid-Based Activity Prediction MethodAntimicrobial Agents and Chemotherapy, 2014
- Structure-based programming of lymph-node targeting in molecular vaccinesNature, 2014
- Tracking and evaluation of dendritic cell migration by cellular magnetic resonance imagingWIREs Nanomedicine and Nanobiotechnology, 2013
- Cross-presentation by dendritic cellsNature Reviews Immunology, 2012
- Interstitial Fluid and Lymph Formation and Transport: Physiological Regulation and Roles in Inflammation and CancerPhysiological Reviews, 2012
- Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migrationCancer Immunology, Immunotherapy, 2008
- The Absorption of Darbepoetin Alfa Occurs Predominantly via the Lymphatics Following Subcutaneous Administration to SheepPharmaceutical Research, 2006
- Th1-Polarizing Capacity of Clinical-Grade Dendritic Cells Is Triggered by Ribomunyl but Is Compromised by PGE2Journal of Immunotherapy, 2005
- Helping the CD8+ T-cell responseNature Reviews Immunology, 2004