Table 1

Survival times of SCID mice after immunoliposomal DXRa treatments

SCID mice (5–7/group) were injected i.v. with 5 million Namalwa cells in 0.2 ml PBS. After 24 h they were injected i.v. in the tail vein with a single bolus dose of 3 mg/kg as free DXR or liposomal DXR. Liposomes were composed of HSPC:Chol:mPEG-DSPE (2:1:0.1) or HSPC:Chol:mPEG-DSPE:Mal-PEG-DSPE (2:1:0.08:0.02). DXR-loaded liposomes targeted with mAbs had 76 μg αCD19/μmol PL (40 molecules of αCD19/liposome) or 70 μg αCD20/μmol PL (37 molecules of αCD20/liposome), respectively. Free mAbs were dosed at 15 μg of αCD19 or 13 μg of αCD20 per mouse, which corresponds to the total amount of mAb received on immunoliposomes. Empty liposomes had 36 molecules of αCD19/liposome or 33 molecules of αCD20/liposome. The combination groups of free mAbs, empty or DXR-loaded liposomes had both components in equal parts. The combination of DXR-loaded αCD19 and αCD20-targeted liposomes was dosed at a total DXR dose of 3 mg/kg, and a total dose of 14 μg free mAbs per mouse.

GroupMean survival time ± SD (days)Percentage increase life spanLong-term survivors (>150 days)
Control (saline)27.6 ± 0.50/5
free DXR31.3 ± 2.7130/5
DXR-HSPC-SL28.6 ± 1.040/5
HSPC-SIL (αCD20)30.5 ± 1.0110/6
HSPC-SIL (αCD19)31.5 ± 2.4140/6
HSPC-SIL (αCD20) + HSPC-SIL (αCD19)33.2 ± 2.0200/6
αCD2034.3 ± 1.1240/6
αCD1934.8 ± 1.0260/6
αCD20 + αCD1940.7 ± 2.0470/6
DXR-HSPC-SL + αCD2033.0 ± 1.3200/6
DXR-HSPC-SL + αCD1939.5 ± 1.0430/6
DXR-HSPC-SIL (αCD20)34.3 ± 4.2240/7
DXR-HSPC-SIL (αCD19)45.7 ± 4.7660/7
DXR-HSPC-SIL (αCD20) + DXR-HSPC-SIL (αCD19)48.6 ± 4.4760/7
  • a DXR, doxorubicin; HSPC, hydrogenated soy phosphatidylcholine; Chol, cholesterol; mPEG-DSPE, methoxy (polyethylene glycol)2000 distearoylphosphatidylethanolamine; Mal-PEG-DSPE, maleimide-derivatized PEG2000-DSPE; mAb, monoclonal antibody; PL, phospholipid; SIL, Stealth immunoliposomes; SL, Stealth liposomes.