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Posted: May 04, 2017

Nanotechnology vaccines in cancer immunotherapy

(Nanowerk Spotlight) Immunotherapy has become an important part of treating some types of cancer. It uses certain parts of a person's immune system to fight the cancer. Usually this is done by administering immune system components, such as man-made immune system proteins.
Tumors evade the immune system by suppressing its ability to recognize and kill cancer cells. The goal of immunotherapy is to normalize and harness the body’s immune system so that it can more effectively fight the tumors.
In recent years, nanotechnology has played an increasingly important role in pursuing efficient vaccine delivery in cancer immunotherapy.
For instance, a proof-of-principle study ("Nanoparticles reprogram immune cells to fight cancer") has shown that nanoparticle-programmed immune cells, known as T cells, can rapidly clear or slow the progression of leukemia in a mouse model.
In another study, researchers had initial success in mice using nanodiscs to deliver a customized therapeutic vaccine for the treatment of colon and melanoma cancer tumors ("Nanodiscs deliver personalized cancer therapy to immune system").
Yet another study showed that magnetic nanoparticles could be key to effective immunotherapy.
In a recent Perspective article in ACS Nano ("Efficient Nanovaccine Delivery in Cancer Immunotherapy"), scientists from the Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, discuss vaccine delivery by synthetic nanoparticles or naturally derived nanoparticles for cancer immunotherapy.
The article looks at how nanotechnology vaccines can efficiently codeliver subunit vaccines, including adjuvants and multiepitope antigens, into lymphoid organs and into antigen-presenting cells, and the intracellular release of vaccine and cross-presentation of antigens can be fine-tuned via nanovaccine engineering. Aside from peptide antigens, antigen-encoding mRNA for cancer immunotherapy delivered by nanovaccine are also discussed.
Schematic depiction of nanovaccine-based vaccine delivery for cancer immunotherapy
Schematic depiction of nanovaccine-based vaccine delivery for cancer immunotherapy. Nanovaccines can be loaded with both adjuvant and multiepitope antigens on the surface (as depicted) or inside nanocarriers. Locally administered nanovaccines efficiently codeliver adjuvant and tumor antigen to secondary lymphoid. (Reprinted with permission by American Chemical Society) (click on image to enlarge)
To execute nanovaccine-based cancer therapy, exogenous nanovaccines can be administered into the body to enable uptake by endogenous phagocytic cells (e.g., dendritic cells, macrophages, monocytes, neutrophils), stimulate innate and adaptive immune cells, and elicit immunity; alternatively, isolated immune cells (e.g., dendritic cells) can be treated with nanovaccines ex vivo, followed by injection of treated cells in vivo for immune modulation.
As the authors write, "chemically defined subunit vaccines can elicit antigen-specific T-cell responses and are relatively easy to manufacture on large scales. However, currently, subunit vaccines have shown limited therapeutic efficacy in humans, which is in part attributed to the poor efficiency of vaccine delivery."
Therefore, nanotechnologies that can efficiently deliver subunit vaccine to secondary lymphoid organs to improve the therapeutic efficacy of vaccines are promising avenues of treatment.
For example, nanovaccines can avoid the otherwise rapid dissemination into the blood circulation and can be drained efficiently into lymph nodes by the lymphatics, which provides a prolonged time window for the nanovaccine to interact with lymph node-residing lymphocytes.
Nanovaccines can also codeliver cancer antigen and adjuvant or multiepitope antigens to induce a broad anticancer T-cell response with minimal immune tolerance.
Further, nanovaccines can be internalized efficiently by antigen-presenting cells, which present antigen to T cells; inside antigen-presenting cells, the nanovaccine can be engineered precisely to release adjuvant and antigen at desired intracellular compartments for optimal cancer immunotherapy.
Nanotechnology vaccines are also expected to facilitate the evaluation and application of cancer therapeutic neoantigen and in vitro transcribed mRNA (IVT-mRNA) antigen, which are two classes of antigens that have recently been extensively explored for cancer immunotherapy.
The scientists point out that this IVT-mRNA vaccine is an emerging candidate enthusiastically pursued for cancer immunotherapy, yet the delivery of naked mRNA, like other therapeutic nucleic acids such as siRNA and plasmids, can be a daunting challenge.
Nanomaterials show promise in improving the efficiency of IVT-mRNA delivery by protecting mRNA from nuclease degradation, enhancing mRNA delivery to lymphoid organs, such as lymph nodes and spleens, and facilitating intracellular delivery of mRNA to antigen-presenting cells.
The authors conclude that "in small animals, a good number of nanovaccines have shown the ability to induce antitumor immunity and can be combined with many other therapeutic modalities for synergistic cancer therapy. It is expected that in the next few years, more types of nanovaccines can be manufactured on large scales and at good manufacturing practice (GMP) grade, and GMP-produced nanovaccines can be tested in humans for safety and therapeutic efficacy."
By . Michael is author of two books by the Royal Society of Chemistry: Nano-Society: Pushing the Boundaries of Technology (RSC Nanoscience & Nanotechnology) and Nanotechnology: The Future is Tiny. Copyright © Nanowerk
 

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