4.15. Development of an Saos2 CDX Model of OS

We found that it was challenging to generate sufficient numbers of mice for in vivo studies when xenografts were established by the direct implantation of Saos2 cell suspensions. While tumors grew, the cell growth kinetics were inconsistent between animals. Therefore, to increase the consistency of tumor take and growth kinetics, a two-step approach was utilized. Saos2 CDX were first established in female NSG (6–8 week old mice) by the implantation of 5 × 10⁶ Saos2 cells (200 µL 1:1 Matrigel to basal RPMI). We found that matching the gender of the tumor sample with the gender of the NSG mice (6–8 weeks old) used for tumor implant improves tumor take and allows for more consistent tumor growth kinetics. Once tumor volumes reached ~1000 mm³, Saos2 tumors were harvested and similar-sized tumor fragments (2 × 2 mm) were implanted into the flank of female NSG mice. Growth kinetics were tracked following implantation by an electronic caliper and implanted mice that showed consistent tumor take and growth kinetics were included in the study. In the re-implanted mice, as soon as the tumor volumes were 100–200 mm³, mice were randomized and treated with four 5-day cycles of SRA737, OTX-015, or combination therapy, as listed above in Figure 8.