The Novel Trifunctional Anti-BCMA NK Cell Engager SAR'514 Has Potent in-Vitro and in-Vivo Anti-Myeloma Effect through Dual NK Cell Engagement

Tang, Alexandre; Gauthier, Laurent; Beninga, Jochen; Rossi, Benjamín; Gourdin, Nicolas; Blanchard-Alvarez, Audrey; Amara, Céline; Courta, Jacqueline; Basset, Alexandra; Bourges, Dorothée; Desjonqueres, Alexandre; Ménoret, Emmanuelle; Pellat‐Deceunynck, Catherine; Moreau, Philippe; Morel, Yannis; Chiron, Marielle; Virone-Oddos, Angela; Vivier, Éric

doi:10.1182/blood-2022-166187

Cited by 4 publications

(2 citation statements)

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“…SAR’514 is a trifunctional molecule that binds BCMA and also activates NK cells through a dual engagement of NKp46 and CD16a. SAR’514 has been shown to promote strong NK cell activity against BCMA+ target MM cells in vitro with very low levels of cytokine release and prolong survival in transgenic mice studies [ 45 ].…”

Section: B Cell Maturation Antigen (Bcma)mentioning

confidence: 99%

Current Novel Targeted Therapeutic Strategies in Multiple Myeloma

Lin,

Tariq,

Ullah

et al. 2024

IJMS

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Multiple myeloma (MM) is a hematologic malignancy caused by the clonal expansion of immunoglobulin-producing plasma cells in the bone marrow and/or extramedullary sites. Common manifestations of MM include anemia, renal dysfunction, infection, bone pain, hypercalcemia, and fatigue. Despite numerous recent advancements in the MM treatment paradigm, current therapies demonstrate limited long-term effectiveness and eventual disease relapse remains exceedingly common. Myeloma cells often develop drug resistance through clonal evolution and alterations of cellular signaling pathways. Therefore, continued research of new targets in MM is crucial to circumvent cumulative drug resistance, overcome treatment-limiting toxicities, and improve outcomes in this incurable disease. This article provides a comprehensive overview of the landscape of novel treatments and emerging therapies for MM grouped by molecular target. Molecular targets outlined include BCMA, GPRC5D, FcRH5, CD38, SLAMF7, BCL-2, kinesin spindle protein, protein disulfide isomerase 1, peptidylprolyl isomerase A, Sec61 translocon, and cyclin-dependent kinase 6. Immunomodulatory drugs, NK cell therapy, and proteolysis-targeting chimera are described as well.

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Section: B Cell Maturation Antigen (Bcma)mentioning

confidence: 99%

Current Novel Targeted Therapeutic Strategies in Multiple Myeloma

Lin,

Tariq,

Ullah

et al. 2024

IJMS

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show abstract

“…On May 2023, a BCMA-targeting ANKET named IPH6401/SAR445514 has entered a phase 1/2 study (NCT05839626) as monotherapy in patients with R/R MM and R/R light chain amyloidosis. Improved NK cell Tapia-Galisteo et al Journal of Hematology & Oncology (2023) 16:83 activation been reported with dual CD16a/NKp46 engagement compared to single CD16a or NKp46 targeting agents or combination of these molecules [126], and cytotoxic activity was only induced in the presence of MM cells and associated with low cytokine release.…”

Section: Dual Targeting Of Nk Cell Activation Receptorsmentioning

confidence: 99%

Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies

Tapia-Galisteo,

Álvarez-Vallina,

Sanz

2023

J Hematol Oncol

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Immune cell engagers are engineered antibodies with at least one arm binding a tumor-associated antigen and at least another one directed against an activating receptor in immune effector cells: CD3 for recruitment of T cells and CD16a for NK cells. The first T cell engager (the anti-CD19 blinatumomab) was approved by the FDA in 2014, but no other one hit the market until 2022. Now the field is gaining momentum, with three approvals in 2022 and 2023 (as of May): the anti-CD20 × anti-CD3 mosunetuzumab and epcoritamab and the anti-B cell maturation antigen (BCMA) × anti-CD3 teclistamab, and another three molecules in regulatory review. T cell engagers will likely revolutionize the treatment of hematological malignancies in the short term, as they are considerably more potent than conventional monoclonal antibodies recognizing the same tumor antigens. The field is thriving, with a plethora of different formats and targets, and around 100 bispecific T cell engagers more are already in clinical trials. Bispecific NK cell engagers are also in early-stage clinical studies and may offer similar efficacy with milder side effects. Trispecific antibodies (engaging either T cell or NK cell receptors) raise the game even further with a third binding moiety, which allows either the targeting of an additional tumor-associated antigen to increase specificity and avoid immune escape or the targeting of additional costimulatory receptors on the immune cell to improve its effector functions. Altogether, these engineered molecules may change the paradigm of treatment for relapsed or refractory hematological malignancies.

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Advances in adoptive cellular immunotherapy and therapeutic breakthroughs in multiple myeloma

Pu,

Liu,

Sharma

et al. 2024

Exp Hematol Oncol

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The basic idea of modulating the immune system to better recognize and fight tumor cells has led to the successful introduction of adoptive cellular immunotherapy (ACT). ACT-based treatment regimens, in which the patient's own immune cells are isolated and subsequently expanded (ex vivo) and reinfused, have also contributed significantly to the development of a personalized treatment strategy. Complementing this, the unprecedented advances in ACTs as chimeric antigen receptor (CAR)-T cell therapies and their derivatives such as CAR-NK, CAR-macrophages, CAR-γδT and CAR-NKT have further maximized the therapeutic outcomes. Herein, we provide a comprehensive overview of the development of ACTs in multiple myeloma (MM) and outline how they have evolved from an experimental form to a mainstay of standard clinical settings. Besides, we provide insights into cytokine-induced killer cell (CIK) therapy, an alternative form of ACT that (as CIK or CAR-CIK) has enormous potential in the clinical spectrum of MM. We also summarize the results of the major preclinical and clinical studies of adoptive cell therapy in MM and address the current challenges (such as cytokine release syndrome (CRS) and neurotoxicity) that limit its complete success in the cancer landscape.

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The Novel Trifunctional Anti-BCMA NK Cell Engager SAR'514 Has Potent in-Vitro and in-Vivo Anti-Myeloma Effect through Dual NK Cell Engagement

Cited by 4 publications

References 0 publications

Current Novel Targeted Therapeutic Strategies in Multiple Myeloma

Current Novel Targeted Therapeutic Strategies in Multiple Myeloma

Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies

Advances in adoptive cellular immunotherapy and therapeutic breakthroughs in multiple myeloma

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