Interleukin-12 as an in situ cancer vaccine component: a review

Cheng, Emily M.; Tsarovsky, Noah; Sondel, Paul M.; Rakhmilevich, Alexander L.

doi:10.1007/s00262-022-03144-1

Cited by 33 publications

(22 citation statements)

References 72 publications

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“…16,[35][36][37] IL-12b plays a role in up-regulating the secretion of IFN-γ, which is considered one of the key factors for tumor regression based on its ability to: inhibit angiogenesis, increase intra-tumoral levels of major histocompatibility molecules (MHC I and II), and promote apoptosis. 30,33,34,[38][39][40] Moreover, IFN-γ augments the differentiation of cytotoxic CD8 + T cells, which are known to have a lethal effect on tumor cells. 28) Consequently, both IFN-γ and IL-12b are considered crucial cytokines for activating adaptive immunity.…”

Section: Resultsmentioning

confidence: 99%

Use of Iontophoresis Technology for Transdermal Delivery of a Minimal mRNA Vaccine as a Potential Melanoma Therapeutic

Husseini

Abe

Hara

et al. 2023

Biological & Pharmaceutical Bulletin

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mRNA vaccines have attracted considerable attention as a result of the 2019 coronavirus pandemic; however, challenges remain regarding use of mRNA vaccines, including insufficient delivery owing to the high molecular weights and high negative charges associated with mRNA. These characteristics of mRNA vaccines impair intracellular uptake and subsequent protein translation. In the current study, we prepared a minimal mRNA vaccine encoding a tumor associated antigen human gp100 25-33 peptide (KVPRNQDWL), as a potential treatment for melanoma. Minimal mRNA vaccines have recently shown promise at improving the translational process, and can be prepared via a simple production method. Moreover, we previously reported the successful use of iontophoresis (IP) technology in the delivery of hydrophilic macromolecules into skin layers, as well as intracellular delivery of small interfering RNA (siRNA). We hypothesized that combining IP technology with a newly synthesized minimal mRNA vaccine can improve both transdermal and intracellular delivery of mRNA. Following IP-induced delivery of a mRNA vaccine, an immune response is elicited resulting in activation of skin resident immune cells. As expected, combining both technologies led to potent stimulation of the immune system, which was observed via potent tumor inhibition in mice bearing melanoma. Additionally, there was an elevation in mRNA expression levels of various cytokines, mainly interferon (IFN)-γ, as well as infiltration of cytotoxic CD8 T cells in the tumor tissue, which are responsible for tumor clearance. This is the first report demonstrating the application of IP for delivery of a minimal mRNA vaccine as a potential melanoma therapeutic.

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Section: Resultsmentioning

confidence: 99%

Use of Iontophoresis Technology for Transdermal Delivery of a Minimal mRNA Vaccine as a Potential Melanoma Therapeutic

Husseini

Abe

Hara

et al. 2023

Biological & Pharmaceutical Bulletin

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“…Compared to the targeted delivery of antigens, in situ vaccination offers neoantigens that are expressed only in the tumor site, which would provide less systemic toxicity and greater immunogenicity. [ 93 ] The in situ vaccination provides tumor‐specific antigens and induces tumor cell death by chemotherapy, oncolytic virus, etc. ; or introduces immune activators (interleukins (IL) like IL‐2, IL‐7, stimulator of interferon gene (STING) agonists, etc.)…”

Section: Nmofs For Cancer Immunotherapymentioning

confidence: 99%

Hybrid Nanomaterials for Cancer Immunotherapy

Yang

et al. 2022

Advanced Science

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Nano-immunotherapy has been recognized as a highly promising strategy for cancer treatment in recent decades, which combines nanotechnology and immunotherapy to combat against tumors. Hybrid nanomaterials consisting of at least two constituents with distinct compositions and properties, usually organic and inorganic, have been engineered with integrated functions and enormous potential in boosting cancer immunotherapy. This review provides a summary of hybrid nanomaterials reported for cancer immunotherapy, including nanoscale metal-organic frameworks, metal-phenolic networks, mesoporous organosilica nanoparticles, metallofullerene nanomaterials, polymer-lipid, and biomacromolecule-based hybrid nanomaterials. The combination of immunotherapy with chemotherapy, chemodynamic therapy, radiotherapy, radiodynamic therapy, photothermal therapy, photodynamic therapy, and sonodynamic therapy based on hybrid nanomaterials is also discussed. Finally, the current challenges and the prospects for designing hybrid nanomaterials and their application in cancer immunotherapy are outlined.

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“…Given the immunosuppression present in tumors and difficulties eliciting immune responses against self-antigens, two studies have also explored including immunostimulatory cytokines in srRNA vaccine vectors have also been included to enhance immunity against encoded antigens. Both of these studies have utilized L-12, a pleiotropic immune stimulatory cytokine, as a means to enhance Th1 immune responses against tumor antigens [56]. In the first study, established were treated by peri-tumoral injection with VRP vectors encoding a P1A, IL-12, or a combination of these vectors [57].…”

Section: Viral Replicon Particles (Vrp) Cancer Vaccinesmentioning

confidence: 99%

Cancer vaccine strategies using self-replicating RNA viral platforms

2022

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The development and success of RNA-based vaccines targeting SARS-CoV-2 has awakened new interest in utilizing RNA vaccines against cancer, particularly in the emerging use of self-replicating RNA (srRNA) viral vaccine platforms. These vaccines are based on different single-stranded RNA viruses, which encode RNA for target antigens in addition to replication genes that are capable of massively amplifying RNA messages after infection. The encoded replicase genes also stimulate innate immunity, making srRNA vectors ideal candidates for anti-tumor vaccination. In this review, we summarize different types of srRNA platforms that have emerged and review evidence for their efficacy in provoking anti-tumor immunity to different antigens. These srRNA platforms encompass the use of naked RNA, DNA-launched replicons, viral replicon particles (VRP), and most recently, synthetic srRNA replicon particles. Across these platforms, studies have demonstrated srRNA vaccine platforms to be potent inducers of anti-tumor immunity, which can be enhanced by homologous vaccine boosting and combining with chemotherapies, radiation, and immune checkpoint inhibition. As such, while this remains an active area of research, the past and present trajectory of srRNA vaccine development suggests immense potential for this platform in producing effective cancer vaccines.

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Interleukin-12 as an in situ cancer vaccine component: a review

Cited by 33 publications

References 72 publications

Use of Iontophoresis Technology for Transdermal Delivery of a Minimal mRNA Vaccine as a Potential Melanoma Therapeutic

Use of Iontophoresis Technology for Transdermal Delivery of a Minimal mRNA Vaccine as a Potential Melanoma Therapeutic

Hybrid Nanomaterials for Cancer Immunotherapy

Cancer vaccine strategies using self-replicating RNA viral platforms

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