Gosset CD3 and FcRH5 Overview
This usually refers to a bispecific therapeutic approach where an antibody or a cell therapy is engineered to simultaneously bind CD3 (on T-cells) and FcRH5 (on malignant plasma cells), promoting immune synapse formation and targeted killing of cancer cells such as in multiple myeloma. CD3 is a multi-subunit signaling component of the T-cell receptor complex, critical for T-cell activation. FcRH5 is a transmembrane receptor predominantly expressed on B-cell lineage cells, especially in multiple myeloma, making it a promising therapeutic target.
Mechanism of Action
Simultaneous engagement of CD3 on T-cells and FcRH5 on malignant plasma cells brings them into close proximity, induces immune synapse formation, triggers TCR signaling, and leads to targeted cell killing primarily via T-cell mediated cytotoxicity (including granzyme/perforin release).
Biological Functions
Disease Associations
Safety Considerations
- Cytokine release syndrome (CRS)
- risk of off-tumor T-cell activation
- immunosuppression with broad CD3 targeting
- risk of B-cell/plasma cell depletion causing hypogammaglobulinemia or infections
- potential off-tumor effects due to low-level expression in normal B-lineage cells
Interacting Drugs
Associated Biomarkers
| Biomarker |
|---|
| T-cell marker (for lymphocyte enumeration and functional assays) |
| FcRH5 expression on plasma cells |
| expression levels may predict drug efficacy |
| T-cell activation markers |