BEAT® the bispecific challenge: a novel and efficient platform for the expression of bispecific IgGs

Moretti, Pierre; Skegro, Darko; Ollier, Romain; Wassmann, Paul; Aebischer, Christel; Laurent, Thibault; Schmid-Printz, Miriam; Giovannini, Roberto; Blein, Stanislas; Bertschinger, Martin

doi:10.1186/1753-6561-7-s6-o9

Cited by 23 publications

(15 citation statements)

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“…GBR1342 is an anti-CD38 × anti-CD3 BsAb, with an Fc domain, an anti-CD38 scFv and an anti-CD3 Fab domain; it has a half-life of ∼5 days in rats (156,157). In human PBMC and MM cell co-cultures (E:T 10:1), GBR1342 demonstrated potent killing of MM cells (157).…”

Section: Gbr1342mentioning

confidence: 99%

Bispecific Antibodies for Multiple Myeloma: A Review of Targets, Drugs, Clinical Trials, and Future Directions

et al. 2020

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Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematological neoplasm in adults, comprising 1.8% of all cancers. With an annual incidence of ∼30,770 cases in the United States, MM has a high mortality rate, leading to 12,770 deaths per year. MM is a genetically complex, highly heterogeneous malignancy, with significant inter-and intra-patient clonal variability. Recent years have witnessed dramatic improvements in the diagnostics, classification, and treatment of MM. However, patients with high-risk disease have not yet benefited from therapeutic advances. Highrisk patients are often primary refractory to treatment or relapse early, ultimately resulting in progression toward aggressive end-stage MM, with associated extramedullary disease or plasma cell leukemia. Therefore, novel treatment modalities are needed to improve the outcomes of these patients. Bispecific antibodies (BsAbs) are immunotherapeutics that simultaneously target and thereby redirect effector immune cells to tumor cells. BsAbs have shown high efficacy in B cell malignancies, including refractory/relapsed acute lymphoblastic leukemia. Various BsAbs targeting MM-specific antigens such as B cell maturation antigen (BCMA), CD38, and CD138 are currently in pre-clinical and clinical development, with promising results. In this review, we outline these advances, focusing on BsAb drugs, their targets, and their potential to improve survival, especially for high-risk MM patients. In combination with current treatment strategies, BsAbs may pave the way toward a cure for MM.

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Section: Gbr1342mentioning

confidence: 99%

Bispecific Antibodies for Multiple Myeloma: A Review of Targets, Drugs, Clinical Trials, and Future Directions

et al. 2020

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“…Антитело GBR 1342 разработано для лечения ММ и должно привлекать Т-лимфоциты к CD38-позитивным опухолевым клеткам. Для разработки антитела использовалась платформа BEAT™ [71]. Полученная таким образом молекула антитела имеет функциональный Fc-фрагмент, один Fabфрагмент и scFv (см.…”

Section: антитела форматов Beat™ и Xmab ®unclassified

Bispecific Antibodies in Clinical Practice and Clinical Trials (Literature Review)

Солопова¹,

Misyurin²

2019

Клиническая онкогематология

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Лечебные моноклональные антитела давно уже стали важным инструментом в руках врачей разных специальностей, прежде всего онкологов. Появление биспецифических антител открыло новые горизонты для лечения рака, стало возможным привлечение собственного иммунитета пациента к борьбе с опухолью. В данном обзоре рассматриваются все форматы и стратегии, использованные при разработке биспецифических антител, дошедших до стадии клинических исследований, а также доступные результаты этих клинических исследований.

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“…One challenge in the development of BsAbs is that of producing correctly paired or assembled materials at sufficient quantity, for both preclinical and clinical development. IgG BsAbs have previously been described in the literature and all of these studies reported the use of transient expression in HEK293 cells for production . However, expression using stable CHO cell lines remains a desired method for the production of biopharmaceutical therapeutics such as antibodies, BsAbs and Fc‐fusion proteins …”

Section: Introductionmentioning

confidence: 99%

“…IgG BsAbs have previously been described in the literature and all of these studies reported the use of transient expression in HEK293 cells for production. [1][2][3][4] However, expression using stable CHO cell lines remains a desired method for the production of biopharmaceutical therapeutics such as antibodies, BsAbs and Fc-fusion proteins. 5,6 Correspondence concerning this article should be addressed to G. C. Barnard at barnard_gavin_c@lilly.com.…”

Section: Introductionmentioning

confidence: 99%

Transient and stable CHO expression, purification and characterization of novel hetero‐dimeric bispecific IgG antibodies

Rajendra

Peery

Hougland

et al. 2017

Biotechnology Progress

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IgG bispecific antibodies (BsAbs) represent one of the preferred formats for bispecific antibody therapeutics due to their native-like IgG properties and their monovalent binding to each target. Most reported studies utilized transient expression in HEK293 cells to produce BsAbs. However, the expression of biotherapeutic molecules using stable CHO cell lines is commonly used for biopharmaceutical manufacturing. Unfortunately, limited information is available in the scientific literature on the expression of BsAbs in CHO cell lines. In this study we describe an alternative approach to express the multiple components of IgG BsAbs using a single plasmid vector (quad vector). This single plasmid vector contains both heavy chain genes and both light chain genes required for the expression and assembly of the IgG BsAb, along with a selectable marker. We expressed, purified, and characterized four different IgG BsAbs or "hetero-mAbs" using transient CHO expression and stable CHO minipools. Transient CHO titers ranged from 90 to 160 mg/L. Stable CHO titers ranged from 0.4 to 2.3 g/L. Following a simple Protein A purification step, the percentage of correctly paired BsAbs ranged from 74% to 98% as determined by mass spectrometry. We also found that information generated from transient CHO expression was similar to information generated using stable CHO minipools. In conclusion, the quad vector approach represents a simple, but effective, alternative approach for the generation of IgG BsAbs in both transient CHO and stable CHO expression systems. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:469-477, 2017.

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BEAT® the bispecific challenge: a novel and efficient platform for the expression of bispecific IgGs

Cited by 23 publications

References 1 publication

Bispecific Antibodies for Multiple Myeloma: A Review of Targets, Drugs, Clinical Trials, and Future Directions

Bispecific Antibodies for Multiple Myeloma: A Review of Targets, Drugs, Clinical Trials, and Future Directions

Bispecific Antibodies in Clinical Practice and Clinical Trials (Literature Review)

Transient and stable CHO expression, purification and characterization of novel hetero‐dimeric bispecific IgG antibodies

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