Phase I study of an active immunotherapy for asymptomatic phase Lymphoplasmacytic lymphoma with DNA vaccines encoding antigen-chemokine fusion: study protocol

Thomas, Sheeba K.; Chul, Soung; Smith, D. Lynne; Kim, Kun Hwa; Parshottam, Sapna; Rao, Sheetal; Popescu, Michael; Lee, Vincent Y.; Neelapu, Sattva S.; Kwak, Larry W.

doi:10.1186/s12885-018-4094-2

Cited by 14 publications

(11 citation statements)

References 34 publications

(26 reference statements)

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“…As an alternative, DNA vaccines could induce immune responses to the encoded antigens and are conceptually safer and more stable than conventional vaccines [11]. Recent advances in antigen designs and delivery methods have greatly enhanced the capacity and applications of DNA vaccines in infectious diseases, cancer, and allergies [12,13,14,15]. The potential clinical value of DNA vaccines for preventing and treating allergies is further highlighted by clinical trials that have demonstrated the safety and tolerability of DNA-based vaccines in patients with human infectious diseases and Japanese red cedar allergies [16,17,18].…”

Section: Introductionmentioning

confidence: 99%

Modulating Shrimp Tropomyosin-Mediated Allergy: Hypoallergen DNA Vaccines Induce Regulatory T Cells to Reduce Hypersensitivity in Mouse Model

Wai

Leung

et al. 2019

IJMS

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Shellfish allergy is one of the most common food allergies, with tropomyosin as the major cross-reactive allergen. However, no allergen-specific immunotherapy is clinically available. Recently, we designed two shrimp hypoallergens MEM49 and MED171. This study aimed to examine and compare the efficacy of the MEM49- and MED171-based DNA vaccines (pMEM49 and pMED171) in modulating shrimp allergy in a murine model of shrimp tropomyosin sensitivity. Intradermal immunization of BALB/c mice with pMEM49 or pMED171 effectively down-modulated allergic symptoms, tropomyosin-specific IgE levels, intestinal Th2 cytokines expression, and inflammatory cell infiltration. Both pMEM49 and pMED171 increased the frequency of regulatory T cells, but to a greater extent by pMED171 with upregulation of gut-homing molecules integrin-α4β7. The functionality of the pMED171-induced Treg cells was further illustrated by anti-CD25-mediated depletion of Treg cells and the adoptive transfer of CD4+CD25+Foxp3+Treg cells. Collectively, the data demonstrate that intradermal administration of pMED171 leads to the priming, activation, and migration of dermal dendritic cells which subsequently induce Treg cells, both locally and systemically, to downregulate the allergic responses to tropomyosin. This study is the first to demonstrate the potency of hypoallergen-encoding DNA vaccines as a therapeutic strategy for human shellfish allergy via the vigorous induction of functional Treg cells.

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Section: Introductionmentioning

confidence: 99%

Modulating Shrimp Tropomyosin-Mediated Allergy: Hypoallergen DNA Vaccines Induce Regulatory T Cells to Reduce Hypersensitivity in Mouse Model

Wai

Leung

et al. 2019

IJMS

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“…In this type of vaccines, the antigen (Id) is expressed in vivo by transfected/infected cells, which could potentiate cellular immune responses, especially when these vectors are targeted to antigen presenting cells. This approach has been validated for B-cell lymphoma in a preclinical mouse model immunized with an adenovirus vector expressing A20 Id 6 and will be tested in clinical trials against B-cell lymphomas using DNA vaccines encoding patient-specific Ids linked to immunostimulatory sequences 29 , 30 . Regarding mRNA vaccines, the recent success of Covid-19 vaccines based on mRNAs expresing the spike protein of SARS-CoV-2, makes this approach very interesting for Id vaccination.…”

Section: Discussionmentioning

confidence: 99%

Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma

Casales

Martišová

Villanueva

et al. 2021

Sci Rep

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A promising therapy for patients with B-cell lymphoma is based on vaccination with idiotype monoclonal antibodies (mAbs). Since idiotypes are different in each tumor, a personalized vaccine has to be produced for each patient. Expression of immunoglobulins with appropriate post-translational modifications for human use often requires the use of stable mammalian cells that can be scaled-up to reach the desired level of production. We have used a noncytopathic self-amplifying RNA vector derived from Semliki Forest virus (ncSFV) to generate BHK cell lines expressing murine follicular lymphoma-derived idiotype A20 mAb. ncSFV/BHK cell lines expressed approximately 2 mg/L/24 h of A20 mAb with proper quaternary structure and a glycosylation pattern similar to that of A20 mAb produced by hybridoma cells. A20 mAb purified from the supernatant of a ncSFV cell line, or from the hybridoma, was conjugated to keyhole limpet hemocyanin and used to immunize Balb/c mice by administration of four weekly doses of 25 µg of mAb. Both idiotype mAbs were able to induce a similar antitumor protection and longer survival compared to non-immunized mice. These results indicate that the ncSFV RNA vector could represent a quick and efficient system to produce patient-specific idiotypes with potential application as lymphoma vaccines.

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“…In current human DNA vaccination approaches antigen-encoding DNA vaccines are coadministered with soluble immunostimulatory agents which often have been approved for anti-tumor adjuvant therapy [ 105 ]. Besides, expression vectors that encode cytokines [ 106 ] or chemokines [ 107 ] are clinically tested. So far, DNA vaccines that integrate both the antigen expression unit and a molecular adjuvant into a single plasmid have been tested in a limited number of studies only.…”

Section: Optimization Of Dna Vaccinesmentioning

confidence: 99%

DNA Vaccines—How Far From Clinical Use?

Hobernik

Bros

2018

IJMS

372

332

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Two decades ago successful transfection of antigen presenting cells (APC) in vivo was demonstrated which resulted in the induction of primary adaptive immune responses. Due to the good biocompatibility of plasmid DNA, their cost-efficient production and long shelf life, many researchers aimed to develop DNA vaccine-based immunotherapeutic strategies for treatment of infections and cancer, but also autoimmune diseases and allergies. This review aims to summarize our current knowledge on the course of action of DNA vaccines, and which factors are responsible for the poor immunogenicity in human so far. Important optimization steps that improve DNA transfection efficiency comprise the introduction of DNA-complexing nano-carriers aimed to prevent extracellular DNA degradation, enabling APC targeting, and enhanced endo/lysosomal escape of DNA. Attachment of virus-derived nuclear localization sequences facilitates nuclear entry of DNA. Improvements in DNA vaccine design include the use of APC-specific promotors for transcriptional targeting, the arrangement of multiple antigen sequences, the co-delivery of molecular adjuvants to prevent tolerance induction, and strategies to circumvent potential inhibitory effects of the vector backbone. Successful clinical use of DNA vaccines may require combined employment of all of these parameters, and combination treatment with additional drugs.

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Phase I study of an active immunotherapy for asymptomatic phase Lymphoplasmacytic lymphoma with DNA vaccines encoding antigen-chemokine fusion: study protocol

Cited by 14 publications

References 34 publications

Modulating Shrimp Tropomyosin-Mediated Allergy: Hypoallergen DNA Vaccines Induce Regulatory T Cells to Reduce Hypersensitivity in Mouse Model

Modulating Shrimp Tropomyosin-Mediated Allergy: Hypoallergen DNA Vaccines Induce Regulatory T Cells to Reduce Hypersensitivity in Mouse Model

Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma

DNA Vaccines—How Far From Clinical Use?

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