Cancer DNA vaccines: current preclinical and clinical developments and future perspectives

Lopes, Alessandra; Vandermeulen, Gaëlle; Préat, Véronique

doi:10.1186/s13046-019-1154-7

Cited by 262 publications

(160 citation statements)

References 147 publications

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“…Thus, studies on its applications to cancer immunotherapy and vaccines are in progress. 103,112) An optimized RNA-LPX showed high spleen-selective gene expression, and antigen-encoding RNA-LPX mediated the rejection of progressive tumors. In that report, the authors compared systemic intravenous vaccine delivery with local subcutaneous delivery.…”

Section: Applications For Spleen Gene Deliverymentioning

confidence: 99%

Lipid Nanoparticles for Cell-Specific in Vivo Targeted Delivery of Nucleic Acids

Khalil

Younis

Kimura

et al. 2020

Biological & Pharmaceutical Bulletin

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The last few years have witnessed a great advance in the development of nonviral systems for in vivo targeted delivery of nucleic acids. Lipid nanoparticles (LNPs) are the most promising carriers for producing clinically approved products in the future. Compared with other systems used for nonviral gene delivery, LNPs provide several advantages including higher stability, low toxicity, and greater efficiency. Additionally, systems based on LNPs can be modified with ligands and devices for controlled biodistribution and internalization into specific cells. Efforts are ongoing to improve the efficiency of lipid-based gene vectors. These efforts depend on the appropriate design of nanocarriers as well as the development of new lipids with improved gene delivery ability. Several ionizable lipids have recently been developed and have shown dramatically improved efficiency. However, enhancing the ability of nanocarriers to target specific cells in the body remains the most difficult challenge. Systemically administered LNPs can access organs in which the capillaries are characterized by the presence of fenestrations, such as the liver and spleen. The liver has received the most attention to date, although targeted delivery to the spleen has recently emerged as a promising tool for modulating the immune system. In this review, we discuss recent advances in the use of LNPs for cellspecific targeted delivery of nucleic acids. We focus mainly on targeting liver hepatocytes and spleen immune cells as excellent targets for gene therapy. We also discuss the potential of endothelial cells as an alternate approach for targeting organs with a continuous endothelium.

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Section: Applications For Spleen Gene Deliverymentioning

confidence: 99%

Lipid Nanoparticles for Cell-Specific in Vivo Targeted Delivery of Nucleic Acids

Khalil

Younis

Kimura

et al. 2020

Biological & Pharmaceutical Bulletin

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“…In recent years, gene therapy with plasmid DNA / RNA vaccines have bright prospects in the prevention and treatment of various cancers. Immunization with these vaccines allows intracellular expression of the encoded immunomodulatory cytokines and can induce a strong humoral and cellular immune response dependent on B and T cells (Burkart et al, 2018; Lopes, Vandermeulen, & Preat, 2019). Despite the infusive efficacy observed in preclinical studies, DNA / RNA vaccines are limited due to the poor immune response and toxicity in humans.…”

Section: In Situ Antitumor Vaccination With Plasmid Dna/rnamentioning

confidence: 99%

In situ antitumor vaccination: Targeting the tumor microenvironment

et al. 2020

Journal Cellular Physiology

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Tumor microenvironment is known to play important roles in tumor progression. Many therapies, targeting the tumor microenvironment, are designed and applied in the clinic. One of these approaches is in situ antitumor therapy. This way, bacteria, antibodies, plasmid DNA, viruses, and cells are intratumorally delivered into the tumor site as “in‐situ antitumor vaccine,” which seeks to enhance immunogenicity and generate systemic T cell responses. In addition, this intratumoral therapy can alter the tumor microenvironment from immunosuppressive to immunostimulatory while limiting the risk of systemic exposure and associated toxicity. Contemporarily, promising preclinical results and some initial success in clinical trials have been obtained after intratumoral therapy.

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“…In the experiment exploring the optimal UPs dosage contained in α-Al 2 O 3 -UPs, BALB/c mice were divided randomly into four groups and, respectively, vaccinated with α-Al 2 O 3 -UPs containing 0, 10, 30 or 100 μg of UPs/mouse. In the experiment exploring the optimal ratio of splenocytes to inactivated 4T1 tumor cells, the splenocytes (1×10 6 cells/well) were, respectively, re-stimulated with 0 (1:0), 1×10 4 (1:0.01), 3×10 4 (1:0.03), 1×10 5 (1:0.1), 3×10 5 (1:0.3), or 1×10 6 (1:1) inactivated 4T1 tumor cells. In the final experiment to compare the immune responses elicited by α-Al 2 O 3 -UPs and α-Al 2 O 3 +UPs, BALB/c mice were divided randomly into three groups, and, respectively, vaccinated with NS, α-Al 2 O 3 +UPs (containing 30 μg UPs) and α-Al 2 O 3 -UPs (containing 30 μg UPs), and the ratio of splenocytes to inactivated 4T1 tumor cells is 1:0.03.…”

Section: Detection Of the Specific Immune Response Elicited By α-Almentioning

confidence: 99%

“…1,5 Among them, therapeutic cancer vaccines are receiving more and more attention attributing to the recent success stories in the clinical treatment of tumors. [6][7][8][9] Therapeutic cancer vaccines are medicines that treat cancers by training the immune system to recognize and attack cancer cells. 10 Thus, tumor-associated antigens (TAAs) which induce specific cytotoxic T lymphocytes (CD8 + CTL) immune response are the vital components of cancer vaccines.…”

Section: Introductionmentioning

confidence: 99%

Anti-Tumor Efficacy of an Adjuvant Built-In Nanovaccine Based on Ubiquitinated Proteins from Tumor Cells

Huang¹,

Zhao²,

Wei³

et al. 2020

IJN

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Background and Aim: We have previously identified ubiquitinated proteins (UPs) from tumor cell lysates as a promising vaccine for cancer immunotherapy in different mouse tumor models. In this study, we aimed at developing a highly efficient therapeutic adjuvant built-in nanovaccine (α-Al 2 O 3-UPs) by a simple method, in which UPs from tumor cells could be efficiently and conveniently enriched by α-Al 2 O 3 nanoparticles covalently coupled with Vx3 proteins (α-Al 2 O 3-CONH-Vx3). Methods: The α-Al 2 O 3 nanoparticles were modified with 4-hydroxybenzoic acid followed by coupling with ubiquitin-binding protein Vx3. It was then used to enrich UPs from 4T1 cell lysate. The stability and the efficiency for the UPs enrichment of α-Al 2 O 3-CONH-Vx3 were examined. The ability of α-Al 2 O 3-UPs to activate DCs was examined in vitro subsequently. The splenocytes from the vaccinated mice were re-stimulated with inactivated tumor cells, and the IFN-γ secretion was detected by ELISA and flow cytometry. Moreover, the therapeutic efficacy of α-Al 2 O 3-UPs, alone and in combination with chemotherapy, was examined in 4T1 tumor-bearing mice. Results: Our results showed that α-Al 2 O 3-UPs were successfully synthesized and abundant UPs from tumor cell lysate were enriched by the new method. In vitro study showed that compared to the physical mixture of α-Al 2 O 3 nanoparticles and UPs (α-Al 2 O 3 +UPs), α-Al 2 O 3-UPs stimulation resulted in higher upregulations of CD80, CD86, MHC class I, and MHC class II on DCs, indicating the higher ability of DC activation. Moreover, α-Al 2 O 3-UPs elicited a more effective immune response in mice, demonstrated by higher IFN-γ secretion than α-Al 2 O 3 +UPs. Furthermore, α-Al 2 O 3-UPs also exhibited a more potent effect on tumor growth inhibition and survival prolongation in 4T1 tumor-bearing mice. Notably, when in combination with low dose chemotherapy, the anti-tumor effect was further enhanced, rather than using α-Al 2 O 3-UPs alone. Conclusion: This study presents an adjuvant built-in nanovaccine generated by a new simple method that can be potentially applied to cancer immunotherapy and lays the experimental foundation for future clinical application.

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Cancer DNA vaccines: current preclinical and clinical developments and future perspectives

Cited by 262 publications

References 147 publications

Lipid Nanoparticles for Cell-Specific <i>in Vivo</i> Targeted Delivery of Nucleic Acids

Lipid Nanoparticles for Cell-Specific <i>in Vivo</i> Targeted Delivery of Nucleic Acids

In situ antitumor vaccination: Targeting the tumor microenvironment

<p>Anti-Tumor Efficacy of an Adjuvant Built-In Nanovaccine Based on Ubiquitinated Proteins from Tumor Cells</p>

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