Tumor regression by repeated intratumoral delivery of water soluble lipopolymers/p2CMVmIL-12 complexes.
The recruitment of the body's own immune system is amongst the most potent defenses known against cancer. Recent attempts to harness this response have enlisted the use of the immune modulating cytokine, interleukin-12 (IL-12). The objective of this work is to investigate the organ distribution and anti-tumor response in vivo after intratumoral administration of IL-12 expression plasmid complexed with water soluble lipopolymer (WSLP). Formulations of WSLP/p2CMVmIL-12 at N/P mol ratio of 20:1 were prepared in the presence of 5% (w/v) glucose. Organ distribution data following intratumoral injection of CT-26 subcutaneous tumor-bearing BALB/c mice demonstrated enhanced retention of WSLP/p2CMVmIL-12 complexes within the tumor and limited accumulation in other organs for up to 96 h. Tumor-bearing BALB/c mice received either single or repeated intratumoral injections at 4- or 8-day intervals to examine the efficacy of single versus repeated injections on tumor regression and survival. Significant tumor growth inhibition during 4- and 8-day injection trials was observed with maximal survival in mice receiving 4-day injections of WSLP/p2CMVmIL-12 complexes. In conclusion, the water-soluble non-toxic lipopolymer complexed with p2CMVIL-12 showed enhanced transgene expression in vivo, inhibits the rate of tumor growth, and significantly increases survival.
Yockman
James W
JW
Department of Pharmaceutics and Pharmaceutical Chemistry, Center for Controlled Chemical Delivery, University of Utah, BPRB, Room 205, Salt Lake City, UT 84112, USA.
Maheshwari
Anurag
A
Han
Sang-oh
SO
Kim
Sung Wan
SW
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003587:Cytomegalovirus / Q000235:genetics; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D015552:Injections, Intralesional; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D008055:Lipids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage; D011108:Polymers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012995:Solubility / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014867:Water / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D008055:Lipids; D011108:Polymers; D014867:Water; D018664:Interleukin-12