Targeted idiotype‐fusion DNA vaccines for human multiple myeloma: preclinical testing

Frøyland, Marianne; Ruffini, Pier Adelchi; Thompson, Keith M.; Gedde‐Dahl, Tobias; Fredriksen, Agnete B.; Bogen, Bjarne

doi:10.1111/j.1600-0609.2011.01590.x

Cited by 10 publications

(22 citation statements)

References 36 publications

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“…Such a possibility was supported by early studies showing that, in DNA vaccinated/electroporated mice, striated muscle cells transfected with immunoglobulin (Ig) heavy (H) and light (L) chain genes secreted complete Ig that was absorbed by targets in vivo [73]. The vaccination strategy with genetic delivery of multi-component fusion proteins has been reported to be successful for Ag fusion proteins directed to APC by use of chemokines [74][75][76] and Ig variable (V) regions [70,[77][78][79][80] even in the absence of adjuvants.…”

Section: Dna Deliverymentioning

confidence: 99%

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Efficient vaccine against pandemic influenza: combining DNA vaccination and targeted delivery to MHC class II molecules

Grødeland¹,

Bogen²

2015

Expert Review of Vaccines

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There are two major limitations to vaccine preparedness in the event of devastating influenza pandemics: the time needed to generate a vaccine and rapid generation of sufficient amounts. DNA vaccination could represent a solution to these problems, but efficacy needs to be enhanced. In a separate line of research, it has been established that targeting of vaccine molecules to antigen-presenting cells enhances immune responses. We have combined the two principles by constructing DNA vaccines that encode bivalent fusion proteins; these target hemagglutinin to MHC class II molecules on antigen-presenting cells. Such DNA vaccines rapidly induce hemagglutinin-specific antibodies and T cell responses in immunized mice. Responses are long-lasting and protect mice against challenge with influenza virus. In a pandemic situation, targeted DNA vaccines could be produced and tested within a month. The novel DNA vaccines could represent a solution to pandemic preparedness in the advent of novel influenza pandemics.

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Section: Dna Deliverymentioning

confidence: 99%

“…A variety of Ags have been introduced with no upper size limit yet having been reached (the largest molecule introduced until now is truncated HA with a size of 523aa, see below). A variety of tumor Ags and infectious Ags have been successfully introduced into the Vaccibody vaccine format [69][70][71]74,77,[79][80][81][82][83].…”

Section: Dna Deliverymentioning

confidence: 99%

Efficient vaccine against pandemic influenza: combining DNA vaccination and targeted delivery to MHC class II molecules

Grødeland¹,

Bogen²

2015

Expert Review of Vaccines

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“…Binding to MHC class II was verified by admixing I-E d -specific VB-containing supernatants and BALB/c (I-E d+ ) A20 B lymphoma cells. Bound VB proteins were detected as previously described [17]. NIP-specific Vaccibodies were tested for their ability to bind to NIP-BSA (conjugated in-house) as previously described [17].…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, DNA Vaccibodies elicited superior antibody and T cell responses in mice, as well as greatly enhanced tumor protection [10,13,15,16]. In a stepwise, translational endeavour, the first fully murine Vaccibodies [10] have been extended to chimeric murine/human Vaccibodies, including tailor-made Vaccibodies for multiple myeloma patients [17]. …”

Section: Introductionmentioning

confidence: 99%

Targeted DNA vaccines eliciting crossreactive anti-idiotypic antibody responses against human B cell malignancies in mice

Ruffini

Dolcetti

et al. 2014

Journal of Translational Medicine

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BackgroundTherapeutic idiotypic (Id) vaccination is an experimental treatment for selected B cell malignancies. A broader use of Id-based vaccination, however, is hampered by the complexity and costs due to the individualized production of protein vaccines. These limitations may be overcome by targeted DNA vaccines encoding stereotyped immunoglobulin V regions of B cell malignancies. We have here investigated whether such vaccines might elicit cross-reactive immune responses thus offering the possibility to immunize subsets of patients with the same vaccine.MethodsFusion vaccines targeting patient Id to mouse Major Histocompatibility Complex (MHC) class II molecules (chimeric mouse/human) or chemokine receptors (fully human) on antigen-presenting cells (APC) were genetically constructed for two Chronic Lymphocytic Leukemia (CLL) patients and one prototypic stereotyped B-cell receptor (BCR) commonly expressed by Hepatitis C Virus (HCV)-associated Non Hodgkin Lymphoma (NHL). The A20 murine B lymphoma cells were engineered to express prototypic HCV-associated B cell lymphoma BCR. Anti-Id antibody responses were studied against stereotyped and non-stereotyped BCRs on CLL patients’ cells as well as transfected A20 cells.ResultsDNA vaccination of mice with Id vaccines that target APC elicited increased amounts of antibodies specific for the patient’s Id as compared with non targeted control vaccines. Anti–Id antibodies cross-reacted between CLL cells with closely related BCR. A20 cells engineered to express patients’ V regions were not tumorigenic in mice, preventing tumor challenge experiments.ConclusionsThese findings provide experimental support for use of APC-targeted fusion Id DNA vaccines for the treatment of B cell lymphoma and CLL that express stereotyped BCRs.

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“…The fusion proteins, called vaccibodies, consist in the variable fragment of an Id single chain (the tumor antigen) and a targeting moiety directed towards antigen-presenting cells (APC), for example the single chain variable fragment of APC-specific antibodies (anti-MHC II, anti-CD40) or chemokines (MIP1α, RANTES) [131][132][133][134]. Structural modifications to vaccibodies, like the generation of bivalent vaccines and the introduction of xenogeneic sequences, further enhanced the effectiveness of the chemokine-Id DNA vaccines [134].…”

Section: Dendritic Cell Vaccinationmentioning

confidence: 99%

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

Binsfeld

Fostier

Muller

et al. 2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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The majority of multiple myeloma patients relapse with the current treatment strategies, raising the need for alternative therapeutic approaches. Cellular immunotherapy is a rapidly evolving field and currently being translated into clinical trials with encouraging results in several cancer types, including multiple myeloma. Murine multiple myeloma models are of critical importance for the development and refinement of cellular immunotherapy. In this review, we summarize the immune cell changes that occur in multiple myeloma patients and we discuss the cell-based immunotherapies that have been tested in multiple myeloma, with a focus on murine models.

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Targeted idiotype‐fusion DNA vaccines for human multiple myeloma: preclinical testing

Abstract: These results pave the way for testing targeted DNA Id vaccines in patients in CR. Id- and patient-specific ELISA could be established affording evaluation of CR depth beyond current serological methods.

Cited by 10 publications

References 36 publications

Efficient vaccine against pandemic influenza: combining DNA vaccination and targeted delivery to MHC class II molecules

Efficient vaccine against pandemic influenza: combining DNA vaccination and targeted delivery to MHC class II molecules

Targeted DNA vaccines eliciting crossreactive anti-idiotypic antibody responses against human B cell malignancies in mice

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

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