Human CLEC12A Stable Cell Line - CHO-K1

Many T-cell engager formats face potential challenges due to extensive engineering, including short serum half-life, immunogenicity, and manufacturing difficulties. To overcome these issues, researchers developed MCLA-117, a CLEC12A×CD3 bispecific antibody utilizing a native human IgG format. MCLA-117 is a full-length human IgG1 bispecific antibody that lacks Fc effector function and incorporates a common light chain (cLC). In the normal hematopoietic system, MCLA-117 binds to cells co-expressing CD3 and CLEC12A but does not bind to early myeloid progenitors or hematopoietic stem cells. MCLA-117 induces T-cell activation and proliferation, triggers the release of mild pro-inflammatory cytokines, and directs T cells to lyse CLEC12A-positive (CLEC12A+) target cells. In co-cultures with T cells, the activity of MCLA-117 against normal CD34-positive (CD34+) cells does not impair erythroid or megakaryocytic differentiation and preserves the development of the monocytic-myeloid lineage. In primary AML (acute myeloid leukemia) patient samples containing autologous T cells, MCLA-117 potently induces the killing of AML blasts, even at low effector-to-target cell ratios.

MCLA-117 is a human full-length IgG1 bispecific antibody based on the "common light chain (cLC) bispecific IgG" format (Figure 1a). Its CLEC12A-targeting cLC Fab fragment was identified via phage display technology, while its CD3-binding cLC Fab fragment was derived from a human anti-CD3 antibody in which the original light chain had been replaced by a common light chain (cLC). To enforce heavy-chain heterodimerization, researchers introduced amino acid residues with opposite charges into the CH3 domains of the two distinct heavy chains. Flow cytometry analysis using tumor cell lines demonstrated that MCLA-117 specifically binds to CLEC12A and CD3 (Figure 1b). Via its CLEC12A-binding arm, the antibody binds to CLEC12A-positive (CLEC12A+) HL60 cells and CHO-K1 cells stably expressing human CLEC12A, but not to parental CHO-K1 cells; via its CD3-binding arm, it binds to CD3-positive (CD3+) Jurkat E6.1 cells, but not to CD3-negative (CD3-) Jurkat J.RT-T3.5 cells.

Figure 1. MCLA-117, a CLEC12AxCD3 full length IgGs bispecific specifically binds to CLEC12A^POS and CD3^POS target cells. (van Loo P F, et al., 2019)