In vitro- and in vivo-targeted tumor lysis by an MMP2 cleavable melittin-LAP fusion protein.

Chemotherapy is one of the main treatment options for cancer, but the effectiveness of chemotherapeutic drugs is severely limited due to their systemic toxicity. Therefore, the need for a more targeted approach in tumor treatment is obvious. A tumor-activated agent would decrease systemic toxicity as well as increase the efficacy of the treatment.

In vivo targeted killing of prostate tumor cells by a synthetic amoebapore helix 3 peptide modified with two γ-linked glutamate residues at the COOH terminus.

We previously designed a pro-cytolytic peptide to target prostate-specific membrane antigen (PSMA)-positive prostate tumor cells. The backbone of the peptide was derived from the cell lytic amoebapore H-3 domain, which becomes completely inactive upon modification by two glutamate residues linked to the ε-amide group of the COOH-terminal lysine through γ-linkages (H-3Glu2). This modified H-3 domain regains its lytic activity against PSMA-positive cells (LNCaP) after the γ-linked glutamate residues are cleaved by PSMA.