Vaccine Delivery Methods into the Future

Apostolopoulos, Vasso

doi:10.3390/vaccines4020009

Cited by 26 publications

(17 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In stark contrast to unmodified HSP70i, which accelerates depigmentation, or to vector DNA, which does not affect disease progression, the HSP70i Q435A eencoding DNA contained and reversed vitiligo in mouse models. For a future clinical application, it became important to select a skin introductory method applicable in patient settings (Apostolopoulos, 2016), and suited for human-like skin (Kim et al, 2012). What is indeed remarkable is the therapeutic success of naked DNA when administered by jet injection, as tested here.…”

Section: Discussionmentioning

confidence: 87%

HSP70iQ435A-Encoding DNA Repigments Vitiligo Lesions in Sinclair Swine

Henning

Fernández

Mahon

et al. 2018

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Human HSP70i carries a single amino-acid modification within the dendritic cell activating region and tolerizes dendritic cells in vitro. The underlying DNA was used to prevent and treat disease in vitiligo mouse models through reduced dendritic cell activation and diminished skin T-cell infiltration, suggesting the same may be useful for patients. Physiologic differences between mouse and human skin then called for studies in large animals with human-like skin. We established the efficiency of DNA jet injection into swine skin before subcloning HSP70i into clinically suitable vector pUMVC3. Vitiligo lesions in Sinclair swine were treated with plasmid DNA to measure changes in depigmentation, T-cell infiltration, expression of HSP70i in skin, serum HSP70i, and anti-HSP70i serum titers. Remarkable repigmentation following HSP70i-encoding DNA treatment persisted throughout the 6-month follow-up period. Repigmentation was accompanied by an initial influx of T cells accompanied by increased CD4/CD8 ratios, waning by week 15. Melanocytes spanned the border of repigmenting skin, suggesting that melanocyte repopulation precedes skin melanization. Serum titer fluctuations were not treatment-associated. Importantly, treatment did not interfere with melanoma immunosurveillance. These data encourage clinical testing of HSP70i.

show abstract

Section: Discussionmentioning

confidence: 87%

HSP70iQ435A-Encoding DNA Repigments Vitiligo Lesions in Sinclair Swine

Henning

Fernández

Mahon

et al. 2018

Journal of Investigative Dermatology

View full text Add to dashboard Cite

show abstract

“…Administration may be enhanced through the use of a gene gun in which DNA/RNA is loaded onto heavy metal-coated nanoparticles that facilitate entry into native antigen-presenting cells such as Langerhans cells. 29 Vaccine potency may be augmented through the presence of bacterial plasmids or CPG or POLY IC sequences that ligate Toll-like receptors (TLRs) and facilitate immune activation. 30,31 In myeloid malignancies, peptide-based vaccine strategies targeting BCR/ABL, WT1, and PR1 have been studied in clinical trials.…”

Section: Single Antigen Peptide-and Protein-based Vaccinesmentioning

confidence: 99%

Vaccine therapy in hematologic malignancies

Avigan

Rosenblatt

2018

Blood

View full text Add to dashboard Cite

Immune-based therapy has emerged as a paradigm shift in cancer therapy with dramatic responses observed in previously incurable disease. Cancer vaccines are being developed to disrupt tumor-associated tolerance and activate and selectively expand tumor-specific lymphocytes within the native effector cell repertoire while maintaining immune-regulatory protection against autoimmunity. Although individual antigen approaches result in immune response with a suggestion of clinical effect in some settings, broader efficacy may be dependent on presentation of multiple antigens that capture clonal diversity presented in the context of functionally potent antigen-presenting cells. The use of whole cell-based strategies such as dendritic cell/tumor fusions have yielded provocative results in single-arm studies and are currently being explored in multicenter randomized trials. The posttransplant setting is a potentially promising platform for vaccination due to cytoreduction and relative depletion of inhibitory accessory cells fostering greater immune responsiveness. Integration of these efforts with other immunotherapeutic strategies and agents that target the tumor microenvironment is being studied in an effort to generate durable immunologic responses with clinically meaningful impact on disease.

show abstract

“…The two DNA vaccines were subsequently evaluated in vivo for their immunogenicity, and pVAX1 empty vector was used as the negative control. As intramuscular injection followed by EP has been reported to improve the immunogenicity of DNA vaccines by enhancing antigen expression and recruiting DCs [16,17], for vaccination in mice, we selected an initial dose of 30 mg DNA per shot.…”

Section: Spd1-fusion Dna Vaccination Enhances Mage-a3specific T Cell mentioning

confidence: 99%

Enhancing the antitumour-specific immunity of a lung DNA vaccine in vivo by fusion expression of MAGE-A3 and soluble PD-1

Chen

Zhang

et al. 2017

Biotechnology & Biotechnological Equipment

View full text Add to dashboard Cite

Although DNA vaccines have shown a good antitumor effect in animal models, they are often not effective in clinical trials. This requires researchers to find an effective way to significantly improve the immunogenicity of vaccines. Here, we developed a new DNA vaccine based on MAGE-A3, which has been suggested as a potential target for lung cancer therapy. We enhanced the potency of this DNA vaccine by overcoming tumour-induced immunosuppressive environment through blockade of the PD-1/PD-L pathway using a soluble PD-1 (sPD1). A series of DNA plasmids encoding MAGE-A3, the extracellular domain of murine PD-1 (sPD1) and their conjugates were constructed and injected into female mice intramuscularly (i.m.) followed by an electric pulse. The humoral and cellular immune responses after immunization were evaluated by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively. To evaluate the therapeutic efficacy of the plasmids, a mouse model with a MAGE-A3-expressing tumour was designed. Mice vaccinated with the fusion expression plasmid generated the strongest MAGE-A3-specific immune responses. Furthermore, these vaccinations inhibited the growth of MAGE-A3-expressing tumours and prolonged mouse survival. These findings suggest that the combination of DNA vaccines with PD-1 pathway inhibitors may be a promising approach in clinical trials. This approach may be viable for vaccines targeting cancer, as anti-tumour vaccines have demonstrated clinical benefit but PD-1 pathway inhibitors alone have demonstrated poor efficacy so far.

show abstract

Vaccine Delivery Methods into the Future

Cited by 26 publications

References 30 publications

HSP70iQ435A-Encoding DNA Repigments Vitiligo Lesions in Sinclair Swine

HSP70iQ435A-Encoding DNA Repigments Vitiligo Lesions in Sinclair Swine

Vaccine therapy in hematologic malignancies

Enhancing the antitumour-specific immunity of a lung DNA vaccine in vivo by fusion expression of MAGE-A3 and soluble PD-1

Contact Info

Product

Resources

About