Safety and efficacy of targeting CD138 with a chimeric antigen receptor for the treatment of multiple myeloma

Sun, Chuang; Mahendravada, Aruna; Ballard, Brandon; Kale, Brandon; Ramos, Carlos A.; West, John A.; Maguire, Todd; McKay, Katie; Lichtman, Eben I.; Tuchman, Sascha A.; Dotti, Gianpietro; Savoldo, Barbara

doi:10.18632/oncotarget.26792

Cited by 75 publications

(54 citation statements)

References 44 publications

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“…In 2019 Sun et al provided data that strongly support the aforementioned clinical trials [105]. They used retroviral vector-mediated transduction of anti-CD138 scFvs from the CD138 antibody (BT062) to develop anti-CD138 CAR T cells.…”

Section: Cd138mentioning

confidence: 96%

Paving the Way toward Successful Multiple Myeloma Treatment: Chimeric Antigen Receptor T-Cell Therapy

Grywalska

Sosnowska‐Pasiarska

Smok-Kalwat

et al. 2020

Cells

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Despite the significant progress of modern anticancer therapies, multiple myeloma (MM) is still incurable for the majority of patients. Following almost three decades of development, chimeric antigen receptor (CAR) T-cell therapy now has the opportunity to revolutionize the treatment landscape and meet the unmet clinical need. However, there are still several major hurdles to overcome. Here we discuss the recent advances of CAR T-cell therapy for MM with an emphasis on future directions and possible risks. Currently, CAR T-cell therapy for MM is at the first stage of clinical studies, and most studies have focused on CAR T cells targeting B cell maturation antigen (BCMA), but other antigens such as cluster of differentiation 138 (CD138, syndecan-1) are also being evaluated. Although this therapy is associated with side effects, such as cytokine release syndrome and neurotoxicity, and relapses have been observed, the benefit–risk balance and huge potential drive the ongoing clinical progress. To fulfill the promise of recent clinical trial success and maximize the potential of CAR T, future efforts should focus on the reduction of side effects, novel targeted antigens, combinatorial uses of different types of CAR T, and development of CAR T cells targeting more than one antigen.

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Section: Cd138mentioning

confidence: 96%

Paving the Way toward Successful Multiple Myeloma Treatment: Chimeric Antigen Receptor T-Cell Therapy

Grywalska

Sosnowska‐Pasiarska

Smok-Kalwat

et al. 2020

Cells

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“…Clinical trials with anti-BCMA CAR-T cells have shown efficacy in certain patients [101]. Other potential targets for CAR-T cell therapy include CD138 [102], CD38 [103], and SLAMF7 [104], which are all cell surface proteins expressed on MM cells. Other strategies include monoclonal antibodies directed to cell surface receptors with current drugs approved for targeting SLAMF7 [105] and BCMA [106].…”

Section: The Intersection Of Llpc and MMmentioning

confidence: 99%

Targeting Multiple Myeloma through the Biology of Long-Lived Plasma Cells

Utley

Lipchick

Lee

et al. 2020

Cancers

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Multiple myeloma (MM) is a hematological malignancy of terminally differentiated bone marrow (BM) resident B lymphocytes known as plasma cells (PC). PC that reside in the bone marrow include a distinct population of long-lived plasma cells (LLPC) that have the capacity to live for very long periods of time (decades in the human population). LLPC biology is critical for understanding MM disease induction and progression because MM shares many of the same extrinsic and intrinsic survival programs as LLPC. Extrinsic survival signals required for LLPC survival include soluble factors and cellular partners in the bone marrow microenvironment. Intrinsic programs that enhance cellular fidelity are also required for LLPC survival including increased autophagy, metabolic fitness, the unfolded protein response (UPR), and enhanced responsiveness to endoplasmic reticulum (ER) stress. Targeting LLPC cell survival mechanisms have led to standard of care treatments for MM including proteasome inhibition (Bortezomib), steroids (Dexamethasone), and immunomodulatory drugs (Lenalidomide). MM patients that relapse often do so by circumventing LLPC survival pathways targeted by treatment. Understanding the mechanisms by which LLPC are able to survive can allow us insight into the treatment of MM, which allows for the enhancement of therapeutic strategies in MM both at diagnosis and upon patient relapse.

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“…Four of them achieved stable disease (SD) and 1 progression (PD). Toxicity of the treatment was limited [8,9].…”

Section: Cd38mentioning

confidence: 99%

Chimeric antigen receptor T in the treatment of multiple myeloma – state of the art and future directions

Dytfeld

2020

Acta Haematologica Polonica

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In spite of the introduction of several new drugs in the last 10 years, multiple myeloma (MM) remains incurable. Thus, an adoptive cellular therapy using chimeric antigen receptor T (CART), a strategy to increase the frequency of tumor-directed and functionally active T cells targeting antigens present on the cancer cell, might change the treatment in MM as it did in lymphoma and ALL. There are several targets for CART therapy in MM on different levels of development, which are discussed in the manuscript. B-cell maturation antigen (BCMA) being tested in the studies of phase 1–2 is the most promising, but so far CART has not been approved in the cure of MM and remains an experimental approach. The hematological society is facing a new technology which with its potential ability to cure MM, in spite of its complexity, cost, and toxicity, will definitely and soon change the landscape of myeloma in Europe and world-wide.

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Safety and efficacy of targeting CD138 with a chimeric antigen receptor for the treatment of multiple myeloma

Cited by 75 publications

References 44 publications

Paving the Way toward Successful Multiple Myeloma Treatment: Chimeric Antigen Receptor T-Cell Therapy

Paving the Way toward Successful Multiple Myeloma Treatment: Chimeric Antigen Receptor T-Cell Therapy

Targeting Multiple Myeloma through the Biology of Long-Lived Plasma Cells

Chimeric antigen receptor T in the treatment of multiple myeloma – state of the art and future directions

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