Figure 5.

Pretreatment with GrB/scFvMEL sensitizes various chemotherapeutic agents. The log-phase gp240 antigen-positive (A375-M) cells were pretreated (at IC₂₅ doses) with various chemotherapeutic agents for 6 hours, followed by the addition of GrB/scFvMEL (IC₂₅). The cells were then incubated for a total of 72 hours (sequence I). Alternatively, cells were first treated with GrB/scFvMEL for 6 hours, and then various chemotherapeutic agents were added for 72 hours (sequence II). Chemotherapeutic agents include DOX, VCR, VP-16, cisplantin (CDDP), Ara C, and 5-FU. The coadministration GrB/scFvMEL and chemotherapeutic agents to A375 cells for 72 hours demonstrated synergistic antitumor activity with DOX, VCR or CDDP, and additive effects, in combination with VP-16 or Ara C or 5-FU. Pretreatment with GrB/scFvMEL for 6 hours, followed by coexposure to these chemotherapeutic agents for 72 hours (II), showed significantly inhibited growth as compared to pretreatment with drugs followed by coexposure to the fusion construct (I).