&lt;p&gt;Immunotherapeutic and Targeted Approaches in Multiple Myeloma&lt;/p&gt;

Nadeem, Omar; Tai, Yu‐Tzu; Anderson, Kenneth C.

doi:10.2147/itt.s240886

Cited by 20 publications

(22 citation statements)

References 110 publications

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“…The past decade has witnessed tremendous progress in immunotherapeutic approaches to myeloma. Authoritative and up-to-date reviews are available ( 29 , 41 ). Current FDA-approved interventions include monoclonal antibodies targeting CD38 [daratumumab ( 42 ), isatuximab ( 43 )] or SLAMF7 [elotuzumab ( 44 )] on the surface of tumor cells.…”

Section: Immunopathology and -Therapy Of Multiple 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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Section: Immunopathology and -Therapy Of Multiple Myelomamentioning

confidence: 99%

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

et al. 2021

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“…And last but not least, CAR T-cells. CAR T-cell transplantation technology has evolved dramatically during the past 25 years ( Figure 1 ) [ 18 , 19 , 20 , 21 , 22 ]. The current version of BCMA-directed CAR T-cell therapy employs a construct with a single-chain variable fragment that recognizes the BCMA antigen, a spacer, an intracellular co-stimulatory signaling domain (often 4-1BB), and a CD3ζ intracellular domain to stimulate T-cell activation upon binding ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

CART-Cell Therapy: Recent Advances and New Evidence in Multiple Myeloma

Martino

Canale

Alati

et al. 2021

Cancers

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Despite the improvement in survival outcomes, multiple myeloma (MM) remains an incurable disease. Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) represents a new strategy for the treatment of relapsed/refractory MM (R/R). In this paper, we describe several recent advances in the field of anti-BCMA CAR T-cell therapy and MM. Currently, available data on anti-BCMA CART-cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated R/R MM patients. Despite this, the main issues remain to be addressed. First of all, a significant proportion of patients eventually relapse. The potential strategy to prevent relapse includes sequential or combined infusion with CAR T-cells against targets other than BCMA, CAR T-cells with novel dual-targeting vector design, and BCMA expression upregulation. Another dark side of CART therapy is safety. Cytokine release syndrome (CRS) andneurologic toxicity are well-described adverse effects. In the MM trials, most CRS events tended to be grade 1 or 2, with fewer patients experiencing grade 3 or higher. Another critical point is the extended timeline of the manufacturing process. Allo-CARs offers the potential for scalable manufacturing for on-demand treatment with shorter waiting days. Another issue is undoubtedly going to be access to this therapy. Currently, only a few academic centers can perform these procedures. Recognizing these issues, the excellent response with BCMA-targeted CAR T-cell therapy makes it a treatment strategy of great promise.

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“…Landmarks in myeloma therapy in the last decade were the development of proteasome inhibitors such as bortezomib and carfilzomib as well as the introduction of immunomodulatory drugs such as thalidomide, lenalidomide, and pomalidomide, which are currently standard of care [ 5 ]. Recently, therapies including monoclonal antibodies against CD38 and B cell maturation antigen (BCMA) as well as CAR T cell therapies reveal promising results [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Multiple Myeloma Inhibitory Activity of Plant Natural Products

Jöhrer

Ҫiҫek

2021

Cancers

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A literature search on plant natural products with antimyeloma activity until the end of 2020 resulted in 92 compounds with effects on at least one human myeloma cell line. Compounds were divided in different compound classes and both their structure–activity-relationships as well as eventual correlations with the pathways described for Multiple Myeloma were discussed. Each of the major compound classes in this review (alkaloids, phenolics, terpenes) revealed interesting candidates, such as dioncophyllines, a group of naphtylisoquinoline alkaloids, which showed pronounced and selective induction of apoptosis when substituted in position 7 of the isoquinoline moiety. Interestingly, out of the phenolic compound class, two of the most noteworthy constituents belong to the relatively small subclass of xanthones, rendering this group a good starting point for possible further drug development. The class of terpenoids also provides noteworthy constituents, such as the highly oxygenated diterpenoid oridonin, which exhibited antiproliferative effects equal to those of bortezomib on RPMI8226 cells. Moreover, triterpenoids containing a lactone ring and/or quinone-like substructures, e.g., bruceantin, whitaferin A, withanolide F, celastrol, and pristimerin, displayed remarkable activity, with the latter two compounds acting as inhibitors of both NF-κB and proteasome chymotrypsin-like activity.

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<p>Immunotherapeutic and Targeted Approaches in Multiple Myeloma</p>

Cited by 20 publications

References 110 publications

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

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

CART-Cell Therapy: Recent Advances and New Evidence in Multiple Myeloma

Multiple Myeloma Inhibitory Activity of Plant Natural Products

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