Ex Vivo Models Simulating the Bone Marrow Environment and Predicting Response to Therapy in Multiple Myeloma

Papadimitriou, Κonstantina; Kostopoulos, Ioannis V.; Tsopanidou, Anastasia; Orologas-Stavrou, Nikolaos; Kastritis, Efstathios; Tsitsilonis, Ourania E.; Terpos, Evangelos

doi:10.3390/cancers12082006

Cited by 15 publications

(19 citation statements)

References 84 publications

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“…This is particularly the case for drug combinations, of which the use of some (Vel/Rev) appear at first sight to be contradictory. Facilitating these studies are recent efforts to use cell lines and patient cells to construct 3D organoids to reconstruct the bone marrow environment [121,122]. These systems are being used to study the pathogenesis of MM [123] and to develop new chemo-and immune therapies [124,125].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Induction Regimes on Immune Responses in Patients with Multiple Myeloma

Firer

Shapira

Luboshits

2021

Cancers

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Current standard frontline therapy for newly diagnosed patients with multiple myeloma (NDMM) involves induction therapy, autologous stem cell transplantation (ASCT), and maintenance therapy. Major efforts are underway to understand the biological and the clinical impacts of each stage of the treatment protocols on overall survival statistics. The most routinely used drugs in the pre-ASCT “induction” regime have different mechanisms of action and are employed either as monotherapies or in various combinations. Aside from their direct effects on cancer cell mortality, these drugs are also known to have varying effects on immune cell functionality. The question remains as to how induction therapy impacts post-ASCT immune reconstitution and anti-tumor immune responses. This review provides an update on the known immune effects of melphalan, dexamethasone, lenalidomide, and bortezomib commonly used in the induction phase of MM therapy. By analyzing the actions of each individual drug on the immune system, we suggest it might be possible to leverage their effects to rationally devise more effective induction regimes. Given the genetic heterogeneity between myeloma patients, it may also be possible to identify subgroups of patients for whom particular induction drug combinations would be more appropriate.

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Section: Discussionmentioning

confidence: 99%

The Impact of Induction Regimes on Immune Responses in Patients with Multiple Myeloma

Firer

Shapira

Luboshits

2021

Cancers

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“…Intravital microscopy and other imaging techniques have been used for studying the relations between normal and malignant hematopoietic cells with their microenvironment [58]. Ex vivo models have also been developed to simulate the BMM and predict the response to treatment [59]. [68][69][70][71][72][73].…”

Section: The Bmm In MMmentioning

confidence: 99%

The Role of Marrow Microenvironment in the Growth and Development of Malignant Plasma Cells in Multiple Myeloma

Giannakoulas

Ntanasis‐Stathopoulos

Terpos

2021

IJMS

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The development and effectiveness of novel therapies in multiple myeloma have been established in large clinical trials. However, multiple myeloma remains an incurable malignancy despite significant therapeutic advances. Accumulating data have elucidated our understanding of the genetic background of the malignant plasma cells along with the role of the bone marrow microenvironment. Currently, the interaction among myeloma cells and the components of the microenvironment are considered crucial in multiple myeloma pathogenesis. Adhesion molecules, cytokines and the extracellular matrix play a critical role in the interplay among genetically transformed clonal plasma cells and stromal cells, leading to the proliferation, progression and survival of myeloma cells. In this review, we provide an overview of the multifaceted role of the bone marrow microenvironment in the growth and development of malignant plasma cells in multiple myeloma.

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“…Care must be taken to select the most appropriate HMCL for a given research question, as significant differences between cell lines exist ( 56 , 57 ). 3D in vitro culture of myeloma cells using a variety of artificial scaffolds is an emerging technology that competes with xenografting and holds promise for drug testing for personalized myeloma therapy ( 58 ).…”

Section: Xenograft Models Of Myelomamentioning

confidence: 99%

Laboratory Mice – A Driving Force in Immunopathology and Immunotherapy Studies of Human Multiple Myeloma

et al. 2021

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Mouse models of human cancer provide an important research tool for elucidating the natural history of neoplastic growth and developing new treatment and prevention approaches. This is particularly true for multiple myeloma (MM), a common and largely incurable neoplasm of post-germinal center, immunoglobulin-producing B lymphocytes, called plasma cells, that reside in the hematopoietic bone marrow (BM) and cause osteolytic lesions and kidney failure among other forms of end-organ damage. The most widely used mouse models used to aid drug and immunotherapy development rely on in vivo propagation of human myeloma cells in immunodeficient hosts (xenografting) or myeloma-like mouse plasma cells in immunocompetent hosts (autografting). Both strategies have made and continue to make valuable contributions to preclinical myeloma, including immune research, yet are ill-suited for studies on tumor development (oncogenesis). Genetically engineered mouse models (GEMMs), such as the widely known Vκ*MYC, may overcome this shortcoming because plasma cell tumors (PCTs) develop de novo (spontaneously) in a highly predictable fashion and accurately recapitulate many hallmarks of human myeloma. Moreover, PCTs arise in an intact organism able to mount a complete innate and adaptive immune response and tumor development reproduces the natural course of human myelomagenesis, beginning with monoclonal gammopathy of undetermined significance (MGUS), progressing to smoldering myeloma (SMM), and eventually transitioning to frank neoplasia. Here we review the utility of transplantation-based and transgenic mouse models of human MM for research on immunopathology and -therapy of plasma cell malignancies, discuss strengths and weaknesses of different experimental approaches, and outline opportunities for closing knowledge gaps, improving the outcome of patients with myeloma, and working towards a cure.

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Ex Vivo Models Simulating the Bone Marrow Environment and Predicting Response to Therapy in Multiple Myeloma

Cited by 15 publications

References 84 publications

The Impact of Induction Regimes on Immune Responses in Patients with Multiple Myeloma

The Impact of Induction Regimes on Immune Responses in Patients with Multiple Myeloma

The Role of Marrow Microenvironment in the Growth and Development of Malignant Plasma Cells in Multiple Myeloma

Laboratory Mice – A Driving Force in Immunopathology and Immunotherapy Studies of Human Multiple Myeloma

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