c-Myc peptide tag on JZQ-B4 adaptor (c-Myc-JZQ-B4)

The c-Myc peptide tag on the JZQ-B4 adaptor is a synthetic target complex used in modular chimeric antigen receptor (CAR) T-cell therapy. The JZQ-B4 component is a high-affinity nanobody (VHH) that specifically binds to Mesothelin (MSLN), a cell-surface glycoprotein overexpressed in various solid tumors, including mesothelioma and ovarian cancer [1, 2]. This nanobody is fused to a c-Myc epitope tag (sequence: EQKLISEEDL), which serves as the recognition site for "universal" CAR-T cells engineered with a c-Myc-specific scFv (typically derived from the 9E10 antibody clone) [1, 3]. By utilizing this adaptor-mediated approach, the activity of the CAR-T cells can be titrated by adjusting the dose of the JZQ-B4 adaptor, providing a safety mechanism to prevent "on-target, off-tumor" toxicity against healthy mesothelial tissues [1, 4]. This system effectively decouples the tumor-recognition phase from the T-cell activation phase, allowing for greater therapeutic flexibility and precision in targeting solid malignancies [1]. The JZQ-B4 nanobody was specifically engineered to be cross-reactive with both human and mouse MSLN, facilitating more accurate preclinical safety and efficacy evaluations in murine models [1].

Other names

Myc-tagged JZQ-B4Mesothelin-targeting c-Myc adaptorJZQ-B4-Myc switchc-Myc-tagged MSLN nanobody

The JZQ-B4 nanobody portion of the adaptor binds to Mesothelin (MSLN) on the surface of tumor cells. The c-Myc peptide tag, located at the C-terminus of the adaptor, is then exposed and recognized by the scFv of a cMyc-specific CAR-T cell. This interaction bridges the T cell and the tumor cell, leading to T-cell activation, cytokine release, and granzyme/perforin-mediated lysis of the MSLN-expressing tumor cell [1, 3].