Combination Immunotherapy of MUC1 mRNA Nano-vaccine and CTLA-4 Blockade Effectively Inhibits Growth of Triple Negative Breast Cancer

Liu, Lina; Wang, Yuhua; Miao, Lei; Liu, Qi; Musetti, Sara; Li, Jun; Huang, Lan

doi:10.1016/j.ymthe.2017.10.020

Cited by 296 publications

(218 citation statements)

References 52 publications

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“…It also analyses the reasons of the successful combination of these two therapies, giving a future perspective on how to optimize anticancer immunotherapies. CTLA4 and PD1 antagonists have been widely used in preclinical and clinical trials due to their ability to enhance tumor-reactive T-cell responses 45 , 46 . However, they are not able to specifically prime T cells and they are toxic in the majority of the patients 47 .…”

Section: Discussionmentioning

confidence: 99%

Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma

Lopes

Vanvarenberg

Kos

et al. 2018

Sci Rep

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DNA vaccination against cancer has become a promising strategy for inducing a specific and long-lasting antitumor immunity. However, DNA vaccines fail to generate potent immune responses when used as a single therapy. To enhance their activity into the tumor, a DNA vaccine against murine P815 mastocytoma was combined with antibodies directed against the immune checkpoints CTLA4 and PD1. The combination of these two strategies delayed tumor growth and enhanced specific antitumor immune cell infiltration in comparison to the corresponding single therapies. The combination also promoted IFNg, IL12 and granzyme B production in the tumor microenvironment and decreased the formation of liver metastasis in a very early phase of tumor development, enabling 90% survival. These results underline the complementarity of DNA vaccination and immune checkpoint blockers in inducing a potent immune response, by exploiting the generation of antigen-specific T cells by the vaccine and the ability of immune checkpoint blockers to enhance T cell activity and infiltration in the tumor. These findings suggest how and why a rational combination therapy can overcome the limits of DNA vaccination but could also allow responses to immune checkpoint blockers in a larger proportion of subjects.

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Section: Discussionmentioning

confidence: 99%

Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma

Lopes

Vanvarenberg

Kos

et al. 2018

Sci Rep

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show abstract

“…This study reports on a nanoparticle platform, named mRNA Galsomes, that successfully co-delivers nucleoside-modified antigen-encoding mRNA and the glycolipid antigen and immunopotentiator α-Galactosylceramide (α-GC) to antigen-presenting cells after Where for long the use of mRNA was limited due to its perceived instability, it is nowadays possible to successfully deliver mRNA in vivo. 1 This is strongly supported by two recent breakthroughs: (i) the packaging of mRNA molecules inside nanoparticles, designed to improve the selective cell targeting and cytosolic delivery of mRNA [2][3][4][5][6][7][8][9] and (ii) the technical progress in the mRNA construct, including the incorporation of modified nucleotides, yielding more stable mRNA with an improved translation capacity. [10][11][12][13] Particularly in the field of vaccination, mRNA encoding antigens has emerged as a versatile and promising platform.…”

mentioning

confidence: 99%

Broadening the Message: A Nanovaccine Co-loaded with Messenger RNA and α-GalCer Induces Antitumor Immunity through Conventional and Natural Killer T Cells

et al. 2019

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Messenger RNA encoding tumor antigens has the potential to evoke effective antitumor immunity. This study reports on a nanoparticle platform, named mRNA Galsomes, that successfully co-delivers nucleoside-modified antigen-encoding mRNA and the glycolipid antigen and immunopotentiator αgalactosylceramide (α-GC) to antigen-presenting cells after intravenous administration. By co-formulating low doses of α-GC, mRNA Galsomes induce a pluripotent innate and adaptive tumorspecific immune response in mice, with invariant natural killer T cells (iNKT) as a driving force. In comparison, mRNA Galsomes exhibit advantages over the state-of-the-art cancer vaccines using unmodified ovalbumin (OVA)-encoding mRNA, as we observed up to seven times more tumor-infiltrating antigen-specific cytotoxic T cells, combined with a strong iNKT cell and NK cell activation. In addition, the presence of suppressive myeloid cells (myeloid-derived suppressor cells and tumor-associated macrophages) in the tumor microenvironment was significantly lowered. Owing to these antitumor effects, OVA mRNA Galsomes significantly reduced tumor growth in established E.G7-OVA lymphoma, with a complete tumor rejection in 40% of the animals. Moreover, therapeutic vaccination with mRNA Galsomes enhanced the responsiveness to treatment with a PD-L1 checkpoint inhibitor in B16-OVA melanoma, as evidenced by a synergistic reduction of tumor outgrowth and a significantly prolonged median survival. Taken together, these data show that intravenously administered mRNA Galsomes can provide controllable, multifaceted, and effective antitumor immunity, especially when combined with checkpoint inhibition.

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“…The vaccine was then injected into mice bearing triple-negative breast cancer together with anti-CTLA-4 antibody. The combined therapy showed better response than either therapies separately [175].…”

Section: Nanoparticles Increase Vaccine Efficacymentioning

confidence: 85%

Nanomedicine and Immunotherapy: A Step Further towards Precision Medicine for Glioblastoma

et al. 2020

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Owing to the advancement of technology combined with our deeper knowledge of human nature and diseases, we are able to move towards precision medicine, where patients are treated at the individual level in concordance with their genetic profiles. Lately, the integration of nanoparticles in biotechnology and their applications in medicine has allowed us to diagnose and treat disease better and more precisely. As a model disease, we used a grade IV malignant brain tumor (glioblastoma). Significant improvements in diagnosis were achieved with the application of fluorescent nanoparticles for intraoperative magnetic resonance imaging (MRI), allowing for improved tumor cell visibility and increasing the extent of the surgical resection, leading to better patient response. Fluorescent probes can be engineered to be activated through different molecular pathways, which will open the path to individualized glioblastoma diagnosis, monitoring, and treatment. Nanoparticles are also extensively studied as nanovehicles for targeted delivery and more controlled medication release, and some nanomedicines are already in early phases of clinical trials. Moreover, sampling biological fluids will give new insights into glioblastoma pathogenesis due to the presence of extracellular vesicles, circulating tumor cells, and circulating tumor DNA. As current glioblastoma therapy does not provide good quality of life for patients, other approaches such as immunotherapy are explored. To conclude, we reason that development of personalized therapies based on a patient’s genetic signature combined with pharmacogenomics and immunogenomic information will significantly change the outcome of glioblastoma patients.

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Combination Immunotherapy of MUC1 mRNA Nano-vaccine and CTLA-4 Blockade Effectively Inhibits Growth of Triple Negative Breast Cancer

Cited by 296 publications

References 52 publications

Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma

Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma

Broadening the Message: A Nanovaccine Co-loaded with Messenger RNA and α-GalCer Induces Antitumor Immunity through Conventional and Natural Killer T Cells

Nanomedicine and Immunotherapy: A Step Further towards Precision Medicine for Glioblastoma

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