Lymph node targeting strategies to improve vaccination efficacy

Jiang, Hao; Wang, Qin; Sun, Xun

doi:10.1016/j.jconrel.2017.08.009

Cited by 232 publications

(234 citation statements)

References 91 publications

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“…PEGylation generally provides an advantage for subcutaneous administration of nano-formulations by promoting their trafficking to draining lymph nodes (dLNs) through drastically reducing interactions between the formulation and cells or serum proteins [33]. To determine the level of particle localization in dLNs at the whole tissue and cellular levels, lysate formulations were labeled with DiD, a lipophilic dye, and administered s.c. at the tail base.…”

Section: Resultsmentioning

confidence: 99%

PEGylated tumor cell membrane vesicles as a new vaccine platform for cancer immunotherapy

et al. 2018

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Despite the promise and advantages of autologous cancer cell vaccination, it remains challenging to induce potent anti-tumor immune responses with traditional immunization strategies with whole tumor cell lysate. In this study, we sought to develop a simple and effective approach for therapeutic vaccination with autologous whole tumor cell lysate. Endogenous cell membranes harvested from cancer cells were formed into PEGylated nano-vesicles (PEG-NPs). PEG-NPs exhibited good serum stability in vitro and draining efficiency to local lymph nodes upon subcutaneous administration in vivo. Vaccination with PEG-NPs synthesized from murine melanoma cells elicited 3.7-fold greater antigen-specific cytotoxic CD8+ T lymphocyte responses, compared with standard vaccination with freeze-thawed lysate in tumor-bearing mice. Importantly, in combination with anti-programmed death-1 (αPD-1) IgG immunotherapy, PEG-NP vaccination induced 4.2-fold higher frequency of antigen-specific T cell responses (P < 0.0001) and mediated complete tumor regression in 63% of tumor-bearing animals (P < 0.01), compared with FT lysate + αPD-1 treatment that exhibited only 13% response rate. In addition, PEG-NPs + αPD-1 IgG combination immunotherapy protected all survivors against a subsequent tumor cell re-challenge. These results demonstrate a general strategy for eliciting anti-tumor immunity using endogenous cancer cell membranes formulated into stable vaccine nanoparticles.

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Section: Resultsmentioning

confidence: 99%

PEGylated tumor cell membrane vesicles as a new vaccine platform for cancer immunotherapy

et al. 2018

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“…In previous studies, melanoma antigen peptide TRP2 was incorporated into polymeric nanoparticles, inorganic nanoparticles, and liposomes and then delivered into lymph nodes for antitumor immunity . In the present study, serum‐derived EXOs were utilized for the delivery of peptide antigen TRP2 into lymph nodes.…”

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confidence: 95%

“…As a result, it may be beneficial to develop carrier systems for delivering peptide antigens to immune cells . To improve the biological performance of peptide antigens as cancer vaccines, biomaterials such as nanoparticles, microparticles, and hydrogels have been used to encapsulate peptides . In particular, nanosized particles have been designed that can deliver antigens and immune stimulators to lymph nodes .…”

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confidence: 99%

“…To boost the immune response, adjuvant molecules such as monophosphoryl lipid A (MPLA) were incorporated into the nanoparticles and delivered along with antigens . The targeted and efficient accumulation of antigens and immune stimulators in lymph nodes is considered a crucial factor for boosting the immune response …”

mentioning

confidence: 99%

“…To ensure successful localization of biomaterials to lymph nodes, the physicochemical properties of the particles, such as the hydrodynamic size and surface charge, should be considered . For example, particles of size 10–100 nm are able to penetrate lymphatic capillaries and accumulate in the lymph nodes, whereas particles below 6 nm tend to drain into the blood vessels . Recently, exosomes (EXOs), naturally‐derived biomaterials with superior stability and biocompatibility, have received much attention for use in the lymphatic targeting of biomolecules.…”

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confidence: 99%

See 2 more Smart Citations

Efficient Delivery of Tyrosinase Related Protein‐2 (TRP2) Peptides to Lymph Nodes using Serum‐Derived Exosomes

Park

Choi

et al. 2018

Macromolecular Bioscience

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Exosomes (EXO) are considered to be versatile carriers for biomolecules; however, the delivery of therapeutic peptides using EXOs poses several challenges. In this study, the efficiency of serum‐derived EXOs in delivering tyrosinase‐related protein‐2 (TRP2) peptides to lymph nodes is determined. TRP2 peptides are successfully incorporated into EXOs, which show a uniform and narrow size distribution of around 45 nm. The TRP2‐incorporated exosomes (EXO‐TRP2) are efficiently internalized into macrophages and dendritic cells, and are seen to display a punctate distribution. EXOs loaded with TRP2 together with MPLA, (EXO‐MPLA‐TRP2) result in a strong release of proinflammatory cytokines (TNF‐α and IL‐6) from both RAW264.7 and DC2.4 cells. Finally, subcutaneous injection of fluorescently labeled EXO‐TRP2 followed by ex vivo imaging using in vivo imaging system (IVIS) show a strong fluorescent signal in the lymph nodes after only 1 h, which is maintained until at least 4 h after injection. Taken together, the findings suggest that serum‐derived EXOs can serve as promising carriers to deliver therapeutic peptides to lymph nodes for immunotherapy.

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Whole‐Cell‐Mimicking Carrier‐Free Nanovaccines Amplify Immune Responses Against Cancer and Bacterial Infection

Qin

Qiao

et al. 2021

Adv Funct Materials

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Whole‐cell vaccines that provide broad‐spectrum antigens have been explored for recent decades. But so far, they have revealed limited success in clinical trials, possibly owing to their inefficiency in targeting immune organs and antigen‐presenting cells (APCs). Herein, a facile strategy is developed to convert the whole‐cell vaccines into the nanoscale size to promote their lymphatic migration and subsequent intracellular antigen presentation to maximize immune responses. Briefly, the study designs a multiple antigen delivery platform based on alum‐induced and cancer/bacterial cell membrane coated protein antigen nanoparticles. Through a simple two‐step vortex‐sonification method, a universal carrier‐free nano‐vaccine without additional excipients could be quickly fabricated. After subcutaneous vaccination, the developed nanovaccines rapidly migrate to lymph nodes, leading to their effective uptake by lymph node‐resident APCs, and subsequent antigen presentation and activation of downstream immune processes. Overall, the described promising work offers a safe, effective, facile, and widely applicable vaccine strategy, which has great potential for clinical transformation.

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Lymph node targeting strategies to improve vaccination efficacy

Cited by 232 publications

References 91 publications

PEGylated tumor cell membrane vesicles as a new vaccine platform for cancer immunotherapy

PEGylated tumor cell membrane vesicles as a new vaccine platform for cancer immunotherapy

Efficient Delivery of Tyrosinase Related Protein‐2 (TRP2) Peptides to Lymph Nodes using Serum‐Derived Exosomes

Whole‐Cell‐Mimicking Carrier‐Free Nanovaccines Amplify Immune Responses Against Cancer and Bacterial Infection

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