Prostate-specific membrane antigen (PSMA)–Cluster of differentiation 3 (CD3)–Cluster of differentiation 28 (CD28) immune synapse (PSMA–CD3–CD28)

The PSMA–CD3–CD28 immune synapse is a synthetic biological interface formed by trispecific T-cell engagers (TriTEs) to facilitate the targeted destruction of prostate cancer cells. This complex is established when a therapeutic agent simultaneously binds to Prostate-Specific Membrane Antigen (PSMA) on the tumor cell surface and the CD3 and CD28 receptors on T-lymphocytes [1, 2]. By co-engaging CD3 (providing Signal 1) and CD28 (providing Signal 2), the synapse triggers a more potent and sustained T-cell activation compared to traditional bispecific antibodies that target CD3 alone [3, 4]. This dual-signaling approach is designed to overcome T-cell anergy and enhance the expansion of effector T-cells within the often-immunosuppressive prostate tumor microenvironment [2, 5]. Clinically, this target is primarily relevant for metastatic castration-resistant prostate cancer (mCRPC), where PSMA is highly expressed [1, 6]. The resulting immune synapse leads to the polarized release of cytotoxic granules, such as perforin and granzymes, inducing apoptosis in the target malignant cell [4, 5].

Other names

PSMA-CD3-CD28 TriTEPSMA-targeted trispecific T-cell engagerPSMA-CD3-CD28 complexSynthetic PSMA-CD3-CD28 synapse

The drug acts as a molecular bridge, bringing T-cells into close proximity with PSMA-expressing tumor cells. It provides simultaneous TCR/CD3 activation (Signal 1) and CD28 co-stimulation (Signal 2), leading to robust T-cell proliferation and cytotoxic activity against the cancer cell [2, 3].