In vivo xenograft ADC efficacy: MDA-MB-231 STn+

The anti-tumor activity of anti-STn ADCs were evaluated as single agents in a MBA-MB-231 STn+ human breast cancer xenograft model. This protocol was reviewed and approved by Translational Drug Development (TD2) (Scottsdale, AZ) Institutional Animal Care and Use Committee (IACUC) and in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80–23, revised 1996). 5×10⁶ tumor cells were injected into the subcutaneous right flank (1:1 Matrigel:media mixture) into 5–8 week old female ICR SCID mice. Tumors were grown to a mean tumor size of 175–225 mm³, and mice were randomly equilibrated by tumor size into 6 groups. Mice were injected intraperitoneally (IP) with 2.5 mg/kg therapeutic antibodies (or vehicle only) once weekly for 3 weeks (Q7Dx3). Group 1 was vehicle control, group 2 was S3F-CL–MMAE, group 3 was 2G12–2B2-CL–MMAE, group 4 was 4G8–1E3-CL–MMAE, group 5 was isotype ADC control MOPC173-CL–MMAE, group 6 was an equal mixture of 2.5 mg/kg unconjugated 2G12–2B2 and 4G8–1E3. Therapeutic ADCs were diluted to appropriate concentration using vehicle control buffer (20 mM citrate + 150 mM NaCl). Tumor volume and body weight were calculated twice weekly and the study end point was when tumor volume exceeded 1000 mm³. Student t-test and %T/C were calculated along with growth curves and percent mouse weight changes to evaluate dose tolerance of the therapies.