KLK2 usually refers to **kallikrein-related peptidase 2**, a prostate-associated serine protease encoded by the human KLK2 gene on chromosome 19.
KLK2 is a secreted, androgen-regulated serine protease produced by prostate epithelial cells that activates PSA and shares about 80% amino acid homology with it.
It is mainly expressed in prostatic tissue and is biologically related to PSA/KLK3, with roles in processing prostatic secretions and activating prostate-specific antigen.
KLK2 is also being studied as a biomarker and therapeutic target in prostate cancer.
Protein: kallikrein-2, is a serine protease.
Major tissue: prostate.
KLK2 is actually expressed on the surface of prostate cancer cells, in both cell lines and patient tumors.
Its expression is more tightly restricted to the prostate than PSMA or STEAP1 — the two other major surface targets currently in use.
That specificity matters clinically: PSMA is also expressed in salivary/lacrimal glands and renal tubules, causing off-tumor toxicity, a problem KLK2-directed drugs are designed to avoid.
Pasritamig is a CD3×KLK2 bispecific T-cell engager, currently the most advanced KLK2 program:
Phase 1 in mCRPC: 42.4% of patients had ≥50% PSA reduction, median radiographic PFS of 7.9 months.
Safety: 9.8% grade 3 treatment-related adverse events; 4 of 45 patients had grade 1 cytokine release syndrome.
When combined with docetaxel in a Phase 1b study, showing a safety profile similar to docetaxel alone plus meaningful PSA responses, supporting a move to Phase 3.
KLK2 is emerging as a next-generation, more tumor-specific alternative/complement to PSMA in advanced prostate cancer, with pasritamig leading the way toward a possible approval.