Bispecific antibody against human BCMA and human CD3

Notification: The cat. code has been changed from bimab-hbcmacd3 to bimab-bcmacd3-05.

Anti-hBCMA-CD3 binds to hCD3 on T cells and to hBCMA on B cells

Monoclonal scFv antibody against human BCMA and human CD3

Anti-hBCMA-CD3 is a bispecific antibody that recognizes two human cell markers: B cell maturation antigen (hBCMA) and hCD3. This antibody features pacanalotamab’s single-chain variable fragments (scFv) joined by a glycine-serine linker and a hexahistidine-tag (His6). Pacanalotamab was developed for the treatment of relapsed/refractory multiple myeloma [1].

 More details

Key features

• Reacts with human BCMA and human CD3
• ScFv of clinical relevant bispecific mAb pacanalotamab
• Hexahistidine (His6) tag
• Provided azide-free
• Each lot is functionally tested

Applications

• Adjustment studies of B cell contact-dependent killing
• Improving T cell activation

InvivoGen also offers an Anti-hCD19-CD3 bispecific antibody as well as other clinically relevant antibodies and their corresponding isotype controls. 

References:

1. Topp et al., 2020. Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma. J Clin Oncol. 2020 Mar 10;38(8):775-783.

Figures

Jurkat-Lucia™ NFAT cell activation upon incubation with Raji hBCMA B cells and Anti-hBCMA-CD3.

Dose-dependent activation of Jurkat-Lucia™ NFAT cells with Anti-hBCMA-CD3 in the presence of Raji cells expressing hBCMA. Raji cells, expressing hBCMA were pre-incubated with increasing concentrations of Anti-hBCMA-CD3 or Anti-hBCMA-bGal (negative control) for 30 minutes before the addition of Jurkat-Lucia™ NFAT cells. After 24 hours of incubation, T cell activation was determined by measuring the Lucia luciferase activity using QUANTI-Luc™ detection reagent. Results are presented as fold change over non-induced cells (mean ± SEM).

Specifications

Clonality: Monoclonal bispecific antibody

Specificity: Targets human BCMA and human CD3

Isotype: none (scFv)

Source: CHO (Chinese hamster ovary) cells

Purity: > 90% Purified by HisTrap affinity chromatography

Tested application: flow cytometry, cellular assay

Quality control:

•    Binding to hBCMA and to hCD3 has been confirmed by flow cytometry.
•    Biological activity has been confirmed using cellular assays.
•    The complete sequence of this antibody has been verified.
•    The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.

Contents

50 µg Anti-hBCMA-CD3, purified antibody, provided azide-free and lyophilized.

 Product is shipped at room temperature.

 Store lyophilized antibody at -20°C.

 Lyophilized product is stable for at least 1 year.

Details

BCMA

Human B cell maturation antigen (BCMA, also known as CD269 or TNFRSF17) is a type III transmembrane glycoprotein playing a central role in B cell maturation and differentiation towards plasma cells [1]. It is expressed on plasma cells, mature B cells as well as multiple myeloma (MM) cells. Interestingly, hBCMA is expressed at similar levels throughout the different stages of MM, which makes it a frequently used target for T cell redirection therapy.

The BiTE^® Molecule AMG 420 , also known as pacanalotamab targeting hCD3 and hBCMA, engages unstimulated T cells to proliferate and subsequently trigger T cell-mediated lysis of hBCMA-positive cells. Thus, antigen presentation is not required, co-stimulation events are bypassed, and T cells remain persistently activated [2].

By interacting with its ligands BAFF (B cell-activating factor) and APRIL (a proliferation-inducing ligand), hBCMA activates several pathways such as NF-κB, AKT, PI3K (phosphoinositide 3-kinase), STAT3, and MAPKT [1, 3]. These various interactions result in enhanced B cell survival and proliferation through the upregulation of anti-apoptotic proteins. Also, it can promote tumor cell growth, survival, and drug resistance [1].

CD3

The cluster of differentiation 3 (CD3, formerly named T3) is a multimeric protein complex consisting of four polypeptides (CD3ε, CD3γ, CD3δ, and CD3ζ) that assemble as three dimers (εγ, εδ, and ζζ) [4]. It is a marker of T cells, which recognizes and participates in the elimination of infected cells and tumor cells through the interaction between the TCR (T cell receptor) on T cells and the MHC-peptide complex on antigen-presenting cells [4-5]. Because of its short cytoplasmic tail, the TCR lacks the ability to signal and requires non-covalent association with the CD3. Upon antigen recognition, the TCR/CD3 complex on T cells triggers downstream intracellular signaling and participates in T cell activation [4].

1. Abramson et al., 2020. B-Cell Maturation Antigen (BCMA) as a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma. Int J Mol Sci. 2020;21(15):5192.
2. Topp et al., 2020. Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma. J Clin Oncol. 2020 Mar 10;38(8):775-783.
3. Hosny et al., 2021. Current State of the Art and Prospects of T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma. J Clin Med. Oct 6;10(19):4593.
4. Chetty R. & Gatter K., 1994. CD3: structure, function, and role of immunostaining in clinical practice. J. Pathol. 173(4):303-307.
5. Smith-Garvin J.E. et al., 2009. T Cell Activation. Ann. Rev. Immunol. 27:591-619.3.