A novel xenograft mouse model for testing approaches targeting human kappa light-chain diseases.

08:00 EDT 29th March 2019 | BioPortfolio

Summary of "A novel xenograft mouse model for testing approaches targeting human kappa light-chain diseases."

Patients with immunoglobulin (Ig) light-chain (LC) diseases such as LC light-chain amyloidosis die with organ failure and need new therapies. We sought a model to test anti-LC siRNA delivery to human plasma cells, requiring circulating LC, in vivo indicators of tumor presence, and capacity for multiple injections of delivery vehicle. The JJN-3 human myeloma reporter cell line expressing firefly luciferase (FFL) implanted intraperitoneally (IP) in the NOD scid γ (NSG) mouse has a 90% prompt tumor-take, rapid LC production, and in vivo indicators of tumor measurable on day 5 post-implant (κ LC, bioluminescent signal, and soluble B-cell maturation antigen [sBCMA]) with median day 5 serum levels of κ LC of 1482 ng/mL (range, 255-4831) and robust correlations with all in vivo indicators. In preliminary attempts to deliver siRNA against κ LC constant region mRNA, we identified the 306-O18B3 lipidoid nanoparticle (LNP) as promising, safe and efficient in vitro. In vivo in the JJN-3 NSG IP model, after daily IP 306-O18B3:siRNA injections on days 5-10, a reduction in κ LC was observed on day 8 between control and test groups that continued through day 12 at sacrifice. This model is potentially useful as a platform for refining anti-LC therapies.


Journal Details

This article was published in the following journal.

Name: Gene therapy
ISSN: 1476-5462


DeepDyve research library

PubMed Articles [31359 Associated PubMed Articles listed on BioPortfolio]

Computational translation of genomic responses from experimental model systems to humans.

The high failure rate of therapeutics showing promise in mouse models to translate to patients is a pressing challenge in biomedical science. Though retrospective studies have examined the fidelity of...

Mice with Chimeric Human Livers and Their Applications.

The complete life cycle of the hepatitis C virus (HCV) can be recapitulated in vivo using immunodeficient mice that have had their livers extensively repopulated with human hepatocytes. These human li...

Advancing nonclinical innovation and safety in pharmaceutical testing.

Nonclinical tests are considered crucial for understanding the safety of investigational medicines. However, the effective translation from nonclinical to human application is limited and must be impr...

MISTRG mice support engraftment and assessment of nonhuman primate hematopoietic stem and progenitor cells.

Pre-clinical feasibility, safety, and efficacy testing of hematopoietic stem cell (HSC)-mediated gene therapy approaches is commonly performed in large animal models such as nonhuman primates (NHPs). ...

Human Xenograft Model.

Human-SCID grafting is a commonly used technique for the long-term investigation of rheumatoid arthritis (RA) explants. To establish a chimeric immunological system in NOD/SCID mice, RA patient-derive...

Clinical Trials [9316 Associated Clinical Trials listed on BioPortfolio]

Role of Chemokine and Chemokine Receptor in Psoriasis

This study aims to elucidate the role of Chemokine and chemokine receptor in the pathogenesis of Psoriasis by using human psoriasis skin xenograft SCID mouse model. The hypothesis is that ...

Patient-Derived Xenograft (PDX) Modeling in Adult Patients With Metastatic or Recurrent Sarcoma

Patients with recurrent or metastatic sarcoma will be consented to develop a patient derived xenograft (PDX or TumorGraft) model of their tumor to perform drug sensitivity testing. The pur...

Study of 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer

DM-CHOC-PEN is a new penclomedine analog that has demonstrated antineoplastic activities in human xenograft intracerebrally implanted tumor mouse models, acceptable preclinical toxicities ...

The EXPLORE Trial: Study Evaluating Xenografts to Personalize Therapies (PDX) in Relapsed Mantle Cell Lymphoma to Optimize Response

The goal of this clinical research study is to use xenograft models to test the effectiveness of certain anti-cancer drugs in relapsed (has come back) or refractory (has not responded to t...

Vaccination of AJCC Stage IIB, IIC, III and IV Melanoma Patients With Human and Mouse Tyrosinase DNA Vaccines

The overall goal of this study is to find out about the safety of injecting the genes (DNA) for human and mouse tyrosinase in patients with melanoma. There is no evidence yet that injectio...

Medical and Biotech [MESH] Definitions

A mouse substrain that is genetically predisposed to the development of systemic lupus erythematosus-like syndrome, which has been found to be clinically similar to the human disease. It has been determined that this mouse strain carries a mutation in the fas gene. Also, the MRL/lpr is a useful model to study behavioral and cognitive deficits found in autoimmune diseases and the efficacy of immunosuppressive agents.

In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.

One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.

A cytoplasmic receptor and peroxin that contains a series of WD40 REPEATS and binds to PEROXISOME TARGETING SIGNAL 2. It is essential for protein import into PEROXISOMES; mutations in the human PEX7 gene are associated with PEROXISOMAL DISORDERS such as Type 1 CHONDRODYSPLASIA PUNCTATA, RHIZOMELIC.

A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc.

Quick Search


DeepDyve research library

Relevant Topics

An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...

Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

Searches Linking to this Article