Due to their ability to elicit a potent immune reaction with low systemic toxicity, cancer vaccines represent a particularly attractive treatment option to either replace or supplement traditional cancer therapies. Such strategies involve the delivery of specific tumor antigens to antigen-presenting cells (APCs). Despite the promise of this approach, the clinical efficacy currently remains modest. Therefore, it is important to explore novel strategies to enhance the in vivo immune reaction stimulated by vaccines for promoted anti-cancer therapy.
Lymph nodes (LNs) are the primary sites of antigen presentation, thus containing a high number of resident APCs, which are adjacent to the initial T cells, so delivery of antigens to LNs is likely to rapidly presented by APCs, resulting in enhanced vaccine efficiency. In addition, resident APCs in LNs are phenotypically immature and capable of internalizing antigens and particles. Thus, LN-resident APCs may be ideal targets for immunotherapeutic cancer vaccines.
Based on this, Profs. NIE Guangjun and ZHAO Ruifang from the National Center for Nanoscience and Technology of the the Chinese Academy of Sciences (CAS) designed a click chemistry-based active lymph node accumulation system (ALAS), which simulated the ligand-receptor interaction, promotes the accumulation of antigen and adjuvant in lymph nodes, thereby enhancing the efficiency of antigen presentation and T cell activation. This study was published in Advanced Materials.
DSPE-PEG (1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)]-2000) is a molecule with good biocompatibility and in vivo safety, which has demonstrated the capacity to efficiently bind to albumin with high affinity and then accumulate in LNs via the intrinsic albumin transport mechanism. Besides, it has been reported that these lipid molecules tend to spontaneously translocate from albumins and insert into the lipid bilayer of cell membranes.
Therefore, the target group-azide (N3) was modified to the hydrophilic terminal of DSPE-PEG, and directional delivery of DSPE-PEG-N3 to LNs along with albumins.
Then, liposomes with the DBCO (dibenzocyclooctyne) group modified on the surface reacted with these azide targets by click chemistry to realize the accumulation of liposomes in lymph nodes.
Finally, the liposome encapsulated antigens and adjuvants were efficiently co-delivered to APCs in the lymph nodes to enhance the tumor antigen-specific CD8+ T cell response.
The ALAS delivered vaccine showed promoted anti-tumor effects in the subcutaneous melanoma model, as well as lung metastatic model, which effectively extended the survival time of tumor-bearing mice.
This work was supported by grants from the National Basic Research Plan of China, the Strategic Priority Research Program of the Chinese Academy of Sciences, the National Natural Science Foundation of China, and the K.C. Wong Education Foundation.
Figure: Schematic illustration of the active lymph-node accumulation cancer vaccine system based on click chemistry
National Center for Nanoscience and Technology