A <scp>CD</scp>138‐independent strategy to detect minimal residual disease and circulating tumour cells in multiple myeloma

Muz, Barbara; Puente, Pilar de la; Azab, Feda; Luderer, Micah John; King, Justin; Vij, Ravi; Azab, Abdel Kareem

doi:10.1111/bjh.13927

Cited by 22 publications

(22 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We also studied the effects of different factors (such as hypoxia or co-culture with stroma) on the expression of CD47 in MM cells. Both hypoxia and stroma were previously shown to change the expression of MM surface biomarkers and sensitivity to therapy [29,36,37]. We found that neither of these had an effect on CD47 expression.…”

Section: Discussionmentioning

confidence: 56%

Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma

Sun

Muz

Alhallak

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

Multiple myeloma (MM) remains to be incurable despite recent therapeutic advances. CD47, an immune checkpoint known as the “don’t eat me” signal, is highly expressed on the surface of various cancers, allowing cancer cells to send inhibitory signals to macrophages and impede phagocytosis and immune response. In this study, we hypothesized that blocking the “don’t eat me” signaling using an anti-CD47 monoclonal antibody will induce killing of MM cells. We report that CD47 expression was directly correlated with stage of the disease, from normal to MGUS to MM. Moreover, MM cells had remarkably higher CD47 expression than other cell populations in the bone marrow. These findings indicate that CD47 is specifically expressed on MM and can be used as a potential therapeutic target. Further, blocking of CD47 using an anti-CD47 antibody induced immediate activation of macrophages, which resulted in induction of phagocytosis and killing of MM cells in the 3D-tissue engineered bone marrow model, as early as 4 hours. These results suggest that macrophage checkpoint immunotherapy by blocking the CD47 “don’t eat me” signal is a novel and promising strategy for the treatment of MM, providing a basis for additional studies to validate these effects in vivo and in patients.

show abstract

Section: Discussionmentioning

confidence: 56%

Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma

Sun

Muz

Alhallak

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

“…Low oxygenation (hypoxia) in the BM microenvironment was shown to occur beyond physiologic BM conditions during the progression of MM and, together with cellular and acellular components, plays a critical role in MM dissemination, stem cell–like properties, and drug resistance [27], [30], [39]. Our research group reported enhanced MM drug resistance to current therapies, including bortezomib and carfilzomib, in hypoxic MM cells [27], [40]. Therefore, targeting hypoxic cells to abolish the drug-resistant cancer population is the vital goal to prevent recurrence in MM patients.…”

Section: Discussionmentioning

confidence: 90%

Selinexor Overcomes Hypoxia-Induced Drug Resistance in Multiple Myeloma

Muz

Azab

Puente

et al. 2017

Translational Oncology

Self Cite

View full text Add to dashboard Cite

Increased levels of the nuclear export protein, exportin 1 (XPO1), were demonstrated in multiple myeloma (MM) patients. Targeting XPO1 with selinexor (the selective inhibitor of nuclear export; SINE compound KPT-330) demonstrates broad antitumor activity also in patient cells resistant to bortezomib; hence, it is a promising target in MM patients. Hypoxia is known to mediate tumor progression and drug resistance (including bortezomib resistance) in MM cells. In this study, we tested the effects of selinexor alone or in combination with bortezomib in normoxia and hypoxia on MM cell survival and apoptosis in vitro and in vivo. In vitro, selinexor alone decreased survival and increased apoptosis, resensitizing MM cells to bortezomib. In vivo, we examined the effects of selinexor alone on tumor initiation and tumor progression, as well as selinexor in combination with bortezomib, on tumor growth in a bortezomib-resistant MM xenograft mouse model. Selinexor, used as a single agent, delayed tumor initiation and tumor progression, prolonging mice survival. In bortezomib-resistant xenografts, selinexor overcame drug resistance, significantly decreasing tumor burden and extending mice survival when combined with bortezomib.

show abstract

“…The characterization of MM by a single surface marker is being questioned over the last decade. CD138, the gold standard surface marker to detect MM cells, is shown to be affected by drug exposure and hypoxia . Other secondary antibodies used in combinations such as CD38, CS1, and CD20 are highly expressed in many other cell types .…”

Section: Future Directionsmentioning

confidence: 99%

“…The EPR effect is an important factor for delivery of nanoparticle systems in general, which has been confirmed mainly for solid tumors. 110 Other secondary antibodies used in combinations such as CD38, CS1, and CD20 are highly expressed in many other cell types. 111 Other markers such as VLA4-4 is expressed in several cell types, and the expression in MM cells is very heterogeneous.…”

Section: Challenges Of Nps For MM Treatmentmentioning

confidence: 99%

Nanoparticle delivery systems, general approaches, and their implementation in multiple myeloma

Puente

Azab

2017

European J of Haematology

Self Cite

View full text Add to dashboard Cite

Multiple myeloma (MM) is a hematological malignancy that remains incurable, with relapse rates greater than 90%. The main limiting factor for the effective use of chemotherapies in MM is the serious side effects caused by these drugs. The emphasis in cancer treatment has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted and rationally designed therapies showing greater efficacy and fewer side effects. Traditional chemotherapy has shown several disadvantages such as lack of targeting capabilities, systemic toxicity and side effects; low therapeutic index, as well as, most anticancer drugs have poor water solubility. Nanoparticle delivery systems (NPs) are capable of targeting large doses of chemotherapies into the target area while sparing healthy tissues, overcoming the limitations of traditional chemotherapy. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to treat multiple myeloma. Many nanoparticle delivery systems have been studied for myeloma using non-targeted NPs (liposomes, polymeric NPs, and inorganic NPs), triggered NPs, as well as targeted NPs (VLA-4, ABC drug transporters, bone microenvironment targeting). The results in preclinical and clinical studies are promising; however, there remains much to be learned in the emerging field of nanomedicine in myeloma.

show abstract

A CD138‐independent strategy to detect minimal residual disease and circulating tumour cells in multiple myeloma

Cited by 22 publications

References 51 publications

Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma

Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma

Selinexor Overcomes Hypoxia-Induced Drug Resistance in Multiple Myeloma

Nanoparticle delivery systems, general approaches, and their implementation in multiple myeloma

Contact Info

Product

Resources

About