Based on prior studies done with recombinant Granzyme B [22], we hypothesized that the replacement of the N-terminal pro-peptides of GZMB and TRP with a peptide substrate that is selectively and efficiency cleaved by PSA [4] would yield zymogens that would be inactive in normal tissues but efficiently activated by high levels of enzymatically active PSA present in the ECF of prostate cancer sites (Figure 1). The gene discussed is KLK3; the disease is prostate cancer.