Prostate-specific membrane antigen (PSMA) and Cluster of differentiation 3 (CD3) (PSMA/CD3)

Prostate-specific membrane antigen (PSMA), also known as Folate Hydrolase 1 (FOLH1), is a type II transmembrane glycoprotein that is highly overexpressed on the surface of prostate cancer cells, especially in metastatic castration-resistant prostate cancer (mCRPC) [2, 13]. Cluster of differentiation 3 (CD3) is a T-cell co-receptor complex essential for the activation of cytotoxic T-cells [4, 11]. The dual targeting of PSMA and CD3 is a therapeutic strategy utilizing bispecific T-cell engagers (BiTEs) or bispecific antibodies to physically bridge T-cells to tumor cells [1, 11]. This interaction facilitates the formation of an immune synapse, leading to the release of cytotoxic granules like perforin and granzymes, which results in the targeted lysis of PSMA-positive cancer cells [4, 11]. While this approach aims to overcome the "cold" immunosuppressive microenvironment of prostate tumors, clinical development has faced hurdles such as cytokine release syndrome (CRS), neurotoxicity, and the development of anti-drug antibodies [8, 10, 14]. Additionally, the efficacy of these agents can be limited by the physical barriers of solid tumors and the potential for on-target, off-tumor binding in tissues like the salivary and lacrimal glands [1, 2, 6].

Other names

FOLH1/CD3Glutamate carboxypeptidase II/CD3GCPII/CD3PSM/CD3PSMAxCD3

Bispecific T-cell engagement; simultaneous binding to PSMA on tumor cells and CD3 on T-cells, leading to T-cell activation and redirected lysis of tumor cells.