Nanotechnology-Based Approaches to Promote Lymph Node Targeted Delivery of Cancer Vaccines

Author(s):  
Ruiqing He ◽  
Jie Zang ◽  
Yuge Zhao ◽  
Haiqing Dong ◽  
Yongyong Li
Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2495
Author(s):  
Kazuhiko Matsuo ◽  
Osamu Yoshie ◽  
Kosuke Kitahata ◽  
Momo Kamei ◽  
Yuta Hara ◽  
...  

Cancer immunotherapy aims to treat cancer by enhancing cancer-specific host immune responses. Recently, cancer immunotherapy has been attracting much attention because of the successful clinical application of immune checkpoint inhibitors targeting the CTLA-4 and PD-1/PD-L1 pathways. However, although highly effective in some patients, immune checkpoint inhibitors are beneficial only in a limited fraction of patients, possibly because of the lack of enough cancer-specific immune cells, especially CD8+ cytotoxic T-lymphocytes (CTLs), in the host. On the other hand, studies on cancer vaccines, especially DC-based ones, have made significant progress in recent years. In particular, the identification and characterization of cross-presenting DCs have greatly advanced the strategy for the development of effective DC-based vaccines. In this review, we first summarize the surface markers and functional properties of the five major DC subsets. We then describe new approaches to induce antigen-specific CTLs by targeted delivery of antigens to cross-presenting DCs. In this context, the chemokine receptor XCR1 and its ligand XCL1, being selectively expressed by cross-presenting DCs and mainly produced by activated CD8+ T cells, respectively, provide highly promising molecular tools for this purpose. In the near future, CTL-inducing DC-based cancer vaccines may provide a new breakthrough in cancer immunotherapy alone or in combination with immune checkpoint inhibitors.


The Analyst ◽  
2017 ◽  
Vol 142 (4) ◽  
pp. 649-659 ◽  
Author(s):  
Ashley E. Ross ◽  
Maura C. Belanger ◽  
Jacob F. Woodroof ◽  
Rebecca R. Pompano

We present the first microfluidic platform for local stimulation of lymph node tissue slices and demonstrate targeted delivery of a model therapeutic.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1068 ◽  
Author(s):  
Danijela Zukancic ◽  
Estelle J. A. Suys ◽  
Emily H. Pilkington ◽  
Azizah Algarni ◽  
Hareth Al-Wassiti ◽  
...  

Targeted delivery of nucleic acids to lymph nodes is critical for the development of effective vaccines and immunotherapies. However, it remains challenging to achieve selective lymph node delivery. Current gene delivery systems target mainly to the liver and typically exhibit off-target transfection at various tissues. Here we report novel lipid nanoparticles (LNPs) that can deliver plasmid DNA (pDNA) to a draining lymph node, thereby significantly enhancing transfection at this target organ, and substantially reducing gene expression at the intramuscular injection site (muscle). In particular, we discovered that LNPs stabilized by 3% Tween 20, a surfactant with a branched poly(ethylene glycol) (PEG) chain linking to a short lipid tail, achieved highly specific transfection at the lymph node. This was in contrast to conventional LNPs stabilized with a linear PEG chain and two saturated lipid tails (PEG-DSPE) that predominately transfected at the injection site (muscle). Interestingly, replacing Tween 20 with Tween 80, which has a longer unsaturated lipid tail, led to a much lower transfection efficiency. Our work demonstrates the importance of PEGylation in selective organ targeting of nanoparticles, provides new insights into the structure–property relationship of LNPs, and offers a novel, simple, and practical PEGylation technology to prepare the next generation of safe and effective vaccines against viruses or tumours.


Author(s):  
Susan N. Thomas

Immunotherapy-based approaches for cancer treatment are of increasing clinical interest. Principles of drug delivery and the emerging field of material design for immunomodulation might hold significant promise for novel approaches in cancer immunotherapy since biomaterials engineering strategies enable enhanced delivery of immune modulatory agents to tissues and cells of the immune system1. One tissue of significant clinical interest in a cancer setting is the tumor-draining lymph node (TDLN), which participates in cancer progression by enabling both metastatic dissemination as well as tumor-induced immune escape. Hence, the TDLN represents a novel target for drug delivery schemes for cancer immunotherapy. We hypothesize that targeted delivery of adjuvants (Adjs) to the TDLN using a biomaterials-based approach might promote antitumor immunity and hinder tumor growth.


Nano Today ◽  
2021 ◽  
Vol 36 ◽  
pp. 101045
Author(s):  
Liwei Jiang ◽  
Sungwook Jung ◽  
Jing Zhao ◽  
Vivek Kasinath ◽  
Takaharu Ichimura ◽  
...  

2015 ◽  
Vol 128 (4) ◽  
pp. 1356-1361 ◽  
Author(s):  
Stefaan De Koker ◽  
Jiwei Cui ◽  
Nane Vanparijs ◽  
Lorenzo Albertazzi ◽  
Johan Grooten ◽  
...  

Biomaterials ◽  
2017 ◽  
Vol 122 ◽  
pp. 105-113 ◽  
Author(s):  
Qin Zeng ◽  
Hanmei Li ◽  
Hao Jiang ◽  
Jiao Yu ◽  
Ying Wang ◽  
...  

2020 ◽  
Author(s):  
Heather Torrey ◽  
Ava Vila-Leahey ◽  
Yuchen Cen ◽  
Danielle MacKay ◽  
Alecia MacKay ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Adham S. Bear ◽  
Conrad R. Cruz ◽  
Aaron E. Foster

The success of cancer vaccines is dependent on the delivery of tumor-associated antigens (TAAs) within lymphoid tissue in the context of costimulatory molecules and immune stimulatory cytokines. Dendritic cells (DCs) are commonly utilized to elicit antitumor immune responses due to their attractive costimulatory molecule and cytokine expression profile. However, the efficacy of DC-based vaccines is limited by the poor viability and lymph-node migration of exogenously generated DCsin vivo. Alternatively, adoptively transferred T cells persist for long periods of timein vivoand readily migrate between the lymphoid and vascular compartments. In addition, T cells may be genetically modified to express both TAA and DC-activating molecules, suggesting that T cells may be ideal candidates to serve as cellular vehicles for antigen delivery to lymph node-resident DCsin vivo. This paper discusses the concept of using T cells to induce tumor-specific immunity for vaccination against cancer.


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