Elotuzumab as a novel anti-myeloma immunotherapy

Radhakrishnan, Sabarinath Venniyil; Bhardwaj, N; Steinbach, Mary; Weidner, Janet; Luetkens, Tim; Atanackovic, Djordje

doi:10.1080/21645515.2017.1327487

Cited by 6 publications

(4 citation statements)

References 31 publications

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“…CD98, also known as LAT1, is expressed in several immune and non-immune cell types in both mouse and human (12)(13)(14)(15)(16)(17)(18). CD319 was found to be expressed by several immune cell types in human (19,20) and SCA-1 is expressed by hematopoietic progenitor cells and is induced in many immune cell types upon type I interferon or TNF stimulation (6,21,22). Thus, specific markers of ASCs are still missing, in particular selective markers of pathogenic ASCs that could serve as selective therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

CD39 and CD326 Are Bona Fide Markers of Murine and Human Plasma Cells and Identify a Bone Marrow Specific Plasma Cell Subpopulation in Lupus

et al. 2022

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Antibody-secreting cells (ASCs) contribute to immunity through production of antibodies and cytokines. Identification of specific markers of ASC would allow selective targeting of these cells in several disease contexts. Here, we performed an unbiased, large-scale protein screening, and identified twelve new molecules that are specifically expressed by murine ASCs. Expression of these markers, particularly CD39, CD81, CD130, and CD326, is stable and offers an improved resolution for ASC identification. We accessed their expression in germ-free conditions and in T cell deficient mice, showing that at least in part their expression is controlled by microbial- and T cell-derived signals. Further analysis of lupus mice revealed the presence of a subpopulation of LAG-3– plasma cells, co-expressing high amounts of CD39 and CD326 in the bone marrow. This population was IgM+ and correlated with IgM anti-dsDNA autoantibodies in sera. Importantly, we found that CD39, CD81, CD130, and CD326 are also expressed by human peripheral blood and bone marrow ASCs. Our data provide innovative insights into ASC biology and function in mice and human, and identify an intriguing BM specific CD39++CD326++ ASC subpopulation in autoimmunity.

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Section: Introductionmentioning

confidence: 99%

CD39 and CD326 Are Bona Fide Markers of Murine and Human Plasma Cells and Identify a Bone Marrow Specific Plasma Cell Subpopulation in Lupus

et al. 2022

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“…TACI is found on human plasma cells, although expression is low in the bone marrow compared to its close relative BCMA . SLAMF7 is highly expressed on human ASCs and multiple myeloma cells, but is also moderately expressed on many immune cells types . The expression of SLAMF7 on natural killer cells has been exploited to develop Elotuzumab, the first approved monoclonal Ab therapy for multiple myeloma that relies on antibody‐dependent cell mediated cytotoxicity directed by natural killer cells against the tumor cells .…”

mentioning

confidence: 99%

“…SLAMF7 is highly expressed on human ASCs and multiple myeloma cells, but is also moderately expressed on many immune cells types . The expression of SLAMF7 on natural killer cells has been exploited to develop Elotuzumab, the first approved monoclonal Ab therapy for multiple myeloma that relies on antibody‐dependent cell mediated cytotoxicity directed by natural killer cells against the tumor cells . In contrast, high CD138 and the loss of CD45 and CD19 occur similarly to the mouse system, although again there are some reports of variation in CD138 expression and the timing of the loss of CD45 and CD19 .…”

mentioning

confidence: 99%

Standing out from the crowd: How to identify plasma cells

Tellier

Nutt

2017

Eur J Immunol

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The differentiation of naïve B cells into plasmablasts and plasma cells (collectively termed antibody-secreting cells (ASCs)) is essential for the production of the protective antibodies (Abs) that enable us to fight infection. This developmental process also provides immunity against re-exposure with the same infectious agent, through the generation of long-lived memory B cells and plasma cells, and is the basis for virtually all currently used vaccination strategies. Defective ASC development and function results in immune deficiency, while inability to elicit long-lived Ab production is a common limitation of vaccine utility. In contrast, excess or inappropriate Ab production drives the pathology associated with some autoimmune conditions such as systemic lupus erythematosus and Sjögrens syndrome [1] and is an important and chronic complication of organ transplantation [2].

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“…SLAMF7 is targeted by the monoclonal antibody elotuzumab, which is approved for the treatment of MM [39].…”

Section: Car-t Targeting Slam-f7mentioning

confidence: 99%

CAR-T cells in multiple myeloma: current status

Steiner¹,

Gunsilius²

2020

memo

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SummaryStarting with the approval of bortezomib, a proteasome-inhibiting drug, tremendous progress has been achieved in the treatment of multiple myeloma (MM) patients during the last 15 years. Due to a plethora of novel drugs such as second generation proteasome inhibitors, immunomodulating agents and monoclonal antibodies the 5‑year survival of MM patients has been extended from 33% at the turn of the millennium to approximately 60% in younger patients (<65–70 years) who were eligible for consolidation with high-dose chemotherapy and autologous stem cell transplantation. Unfortunately, virtually all patients suffer from relapse and ultimately succumb to the disease, indicating the need for additional treatment strategies. Currently there are two promising immunologic approaches. First, bispecific antibodies called BITE (bispecific T-cell enhancer), which act as fusion proteins with two single-chain variable fragments, target antigens on malignant cells and bind the CD3 receptor and thereby recruit T‑cells to the target cells. The second strategy is chimeric antigen receptor (CAR) engineered T‑cell therapy that attacks myeloma cells by recognizing specific targets such as CD138, BCMA (B-cell maturation antigen), light-chains, SLAM-F7 (signaling lymphocytic activation molecule family member 7) or the pan B‑cell antigen CD19.Several early phase clinical trials show encouraging results in patients who have relapsed after modern treatment including proteasome inhibitors, immunomodulating drugs and monoclonal antibodies. Here, we briefly summarize current clinical knowledge about CAR‑T cell treatment in multiple myeloma, including clinical data presented at the 61st American Society of Hematology annual meeting held in December 2019 in Orlando.

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Elotuzumab as a novel anti-myeloma immunotherapy

Cited by 6 publications

References 31 publications

CD39 and CD326 Are Bona Fide Markers of Murine and Human Plasma Cells and Identify a Bone Marrow Specific Plasma Cell Subpopulation in Lupus

CD39 and CD326 Are Bona Fide Markers of Murine and Human Plasma Cells and Identify a Bone Marrow Specific Plasma Cell Subpopulation in Lupus

Standing out from the crowd: How to identify plasma cells

CAR-T cells in multiple myeloma: current status

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