Estimation of MTD

Dose Escalation Study

1. Acclimatize tumor-free female 8-week old 129/Sv mice for a week after arrival
2. Randomize into groups of three mice each the following week
3. Administer a total of 4 doses (on days 1, 5, 8, and 12) of either of the formulations intravenously:
   1. Normal saline (n=3)
   2. Resiquimod PM (n=9)
      1. Resiquimod PM at a dose of 1mg/kg (n=3)
      2. Resiquimod PM at a dose of 3mg/kg (n=3)
      3. Resiquimod PM at a dose of 5mg/kg (n=3)
   3. C₆CP/AZD7762 PM (POx micelles coloaded with C₆CP and AZD7762 at a weight ratio of 10/20) (n=9)
      1. C₆CP/AZD7762 PM at a final dose of 2.5 mg/kg of C₆CP and 5 mg/kg of AZD7762; n=3
      2. C₆CP/AZD7762 PM at a final dose of 5 mg/kg of C₆CP and 10 mg/kg of AZD7762; n=3
      3. C₆CP/AZD7762 PM at a final dose of 10 mg/kg of C₆CP and 20 mg/kg of AZD7762; n=3
   4. C₆CP/VE-822 PM (POx micelles coloaded with C₆CP and VE-822 at a weight ratio of 10/10) (n=9) 
      1. C₆CP/VE-822 PM at a final dose of 5 mg/kg of C₆CP and 5 mg/kg of VE-822; n=3
      2. C₆CP/VE-822 PM at a final dose of 7.5 mg/kg of C₆CP and 7.5 mg/kg of VE-822; n=3
      3. C₆CP/VE-822 PM at a final dose of 10 mg/kg of C₆CP and 10 mg/kg of VE-822; n=3
4. Monitor the animals every other day and record the weight of the animal and euthanize the animals if it meets any of the following criteria: movement impairment, a sign of pain, discomfort or distress, hunchback, matted hair, diarrhea, and a bodyweight loss of greater than 15%.