Preclinical animal models of multiple myeloma

Lwin, Seint T.; Edwards, Claire; Silbermann, Rebecca

doi:10.1038/bonekey.2015.142

Cited by 36 publications

(38 citation statements)

References 47 publications

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“…Moreover, conventional nanoparticle-antibody constructs have demonstrated circulation times on the order of hours, have achieved minimal tumor-uptake via passive modes of targeting, and have been shown to be largely distributed to organs of the reticuloendothelial system due to uptake by resident macrophages that clear them from the circulation. 22 Most pre-clinical studies with such agents have further been conducted in subcutaneous xenograft models 23,24 that do not recapitulate the vascular patterns found in the natural tumor environment; 25,26 not surprisingly, many of these constructs have exhibited no differences when compared to their untargeted counterparts with respect to their in situ relaxivity values, their required systemic doses, and/or their ability to achieve tumor localization, 13 which has stymied their further clinical development. To circumvent these challenges and to develop antibody-targeted nanoparticles that exhibit high sensitivity and specificity for malignant plasma cells, we fabricated ultra-small, sub-5 nm nanoparticles (NPs) that were conjugated to antibodies against the signaling lymphocytic activation molecule-F7 (SLAMF7) or the B-cell maturation antigen (BCMA).…”

Section: Introductionmentioning

confidence: 99%

Antibody-targeting of ultra-small nanoparticles enhances imaging sensitivity and enables longitudinal tracking of multiple myeloma

Detappe

Reidy

et al. 2019

Nanoscale

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Section: Introductionmentioning

confidence: 99%

Antibody-targeting of ultra-small nanoparticles enhances imaging sensitivity and enables longitudinal tracking of multiple myeloma

Detappe

Reidy

et al. 2019

Nanoscale

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“…Animal models do offer the possibility to assess therapeutic responses of novel drugs on human primary myeloma cells grown in a xenogeneic or humanized 3D environment. 13,14 However, animal models are timeconsuming, expensive, and have limited capacity for drug sensitivity testing. 3D in vitro models offer the possibility to culture myeloma cells in a system that resembles the human BM environment closely, in which both therapeutic impact and nonspecific effects can be analyzed.…”

Section: Introductionmentioning

confidence: 99%

Liposomal drug delivery in an in vitro 3D bone marrow model for multiple myeloma

Braham¹,

Deshantri²,

Minnema³

et al. 2018

IJN

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PurposeLiposomal drug delivery can improve the therapeutic index of treatments for multiple myeloma. However, an appropriate 3D model for the in vitro evaluation of liposomal drug delivery is lacking. In this study, we applied a previously developed 3D bone marrow (BM) myeloma model to examine liposomal drug therapy.Material and methodsLiposomes of different sizes (~75–200 nm) were tested in a 3D BM myeloma model, based on multipotent mesenchymal stromal cells, endothelial progenitor cells, and myeloma cells cocultured in hydrogel. The behavior and efficacy of liposomal drug therapy was investigated, evaluating the feasibility of testing liposomal drug delivery in 3D in vitro. Intracellular uptake of untargeted and integrin α4β1 (very late antigen-4) targeted liposomes was compared in myeloma and supporting cells, as well as the effectivity of free and liposome-encapsulated chemotherapy (bortezomib, doxorubicin). Either cocultured myeloma cell lines or primary CD138+ myeloma cells received the treatments.ResultsLiposomes (~75–110 nm) passively diffused throughout the heterogeneously porous (~80–850 nm) 3D hydrogel model after insertion. Cellular uptake of liposomes was observed and was increased by targeting very late antigen-4. Liposomal bortezomib and doxorubicin showed increased cytotoxic effects toward myeloma cells compared with the free drugs, using either a cell line or primary myeloma cells. Cytotoxicity toward supporting BM cells was reduced using liposomes.ConclusionThe 3D model allows the study of liposome-encapsulated molecules on multiple myeloma and supporting BM cells, looking at cellular targeting, and general efficacy of the given therapy. The advantages of liposomal drug delivery were demonstrated in a primary myeloma model, enabling the study of patient-to-patient responses to potential drugs and treatment regimes.

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“…The use of animal models for the study of tumor‐induced bone disease is well established. A wide variety of models exist employing tumor cell types from diverse origins and host environments with a range of backgrounds, including normal healthy animals to aged or immunocompromised mice . By our estimates, over 8000 animals/year are used to model the interactions of the tumor–bone niche worldwide, despite a range of reliable surrogates that mimic the various cellular and matrix components of this system and where the human tumor–bone niche may be recapitulated ex vivo as an alternative first‐line assay to the use of animal models in the study of cancer–bone disease.…”

Section: Discussionmentioning

confidence: 99%

Modeling the Human Bone–Tumor Niche: Reducing and Replacing the Need for Animal Data

Rao

Edwards

2020

JBMR Plus

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Bone is the most common site for cancer metastasis. Understanding the interactions within the complex, heterogeneous bone–tumor microenvironment is essential for the development of new therapeutics. Various animal models of tumor‐induced bone disease are routinely used to provide valuable information on the relationship between cancer cells and the skeleton. However, new model systems exist that offer an alternative approach to the use of animals and might more accurately reveal the cellular interactions occurring within the human bone–tumor niche. This review highlights replacement models that mimic the bone microenvironment and where cancer metastases and tumor growth might be assessed alongside bone turnover. Such culture models include the use of calcified regions of animal tissue and scaffolds made from bone mineral hydroxyapatite, synthetic polymers that can be manipulated during manufacture to create structures resembling trabecular bone surfaces, gel composites that can be modified for stiffness and porosity to resemble conditions in the tumor–bone microenvironment. Possibly the most accurate model system involves the use of fresh human bone samples, which can be cultured ex vivo in the presence of human tumor cells and demonstrate similar cancer cell–bone cell interactions as described in vivo. In addition, the use of mathematical modeling and computational biology approaches provide an alternative to preliminary animal testing. The use of such models offers the capacity to mimic significant elements of the human bone–tumor environment, and complement, refine, or replace the use of preclinical models. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Preclinical animal models of multiple myeloma

Cited by 36 publications

References 47 publications

Antibody-targeting of ultra-small nanoparticles enhances imaging sensitivity and enables longitudinal tracking of multiple myeloma

Antibody-targeting of ultra-small nanoparticles enhances imaging sensitivity and enables longitudinal tracking of multiple myeloma

Liposomal drug delivery in an in vitro 3D bone marrow model for multiple myeloma

Modeling the Human Bone–Tumor Niche: Reducing and Replacing the Need for Animal Data

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