Figure 7.
Life extension graphs (Kaplan–Meier survival curves) for tumor-bearing mice treated with either Taxol or its octaarginine derivatives.61 (A) One × 107 UCI-101 tumor cells expressing luciferase were implanted into the peritoneal cavity of athymic nu/nu mice 7 days before treatment. Mice were treated with IP injections of 5 (left) or 10 mg/kg (right) of Taxol or equimolar amounts of its derivatives [octaarginine conjugated to C2′, 2a or C7, 3a, positions] on days 0, 5, and 10. Tumor burden was monitored by bioluminescence imaging (n = 8 per group). C2′ conjugate, 2a, produces significantly greater survival than Taxol at both 5 mg/kg (P = 0.0039) and 10 mg/kg (P = 0.047). (B) Taxol-sensitive (OVCA-429) and Taxol-resistant (OVCA-429T) cancers, when treated with free Taxol and releasable Taxol–transporter conjugates. Mice were implanted with 1 × 107 OVCA-429 or OVCA-429T cells expressing luciferase and subsequently treated (7 days later) with 5 mg/kg of Taxol or equimolar amounts of an octaarginine C7-conjugated derivative 3a on days 0, 5, and 10. Tumor burden was measured by bioluminescence imaging (n = 8 per group). The octaarginine conjugate 3a produces significantly better survival rates than Taxol in OVCA-429T cells (P = 0.0002). Reproduced with permission from ref (61). Copyright 2008 National Academy of Sciences.