Hi Amateur:
If Novartis done their own study on 2503, maybe they will consider liposomal formulation as next step.
mz
From :
aacr98.expocity.com
[PROC. AMER. ASSOC. CANCER RES. 39, March 1998]
Copyright c 1998 by the American Association for Cancer Research
#2836 Liposome formulation improves efficacy against xenografted human tumor lines in nude mice, and alters
pharmacokinetics of an antisense oligonucleotide inhibitor of H-ras expression. Cooper, S., Howard, R., Glazer, R., Trent,
K., Leamon, C. P., Mehta, R., Ohashi, C., Cowsert, L., Monia, B P., & Dean, N. M. ISIS Pharmaceuticals, 2280 Faraday
Ave., Carlsbad, CA 92008
The most commonly occuring mutated oncogenes in human tumors are members of the p21 or ras family of genes. Three members
of this family are known to exist, H-ras, K-ras and N-ras. The importance of the ras family in regulating abnormal growth has
made these genes important targets against which to develop novel therapeutic agents. We have previously identified an antisense
oligonucleotide targeting H-ras (ISIS 2503) which is a potent and specific inhibitor of H-ras expression in tissue culture cells. When
formulated in saline, this oligonucleotide inhibits the growth of a number of human tumor cell lines grown in nude mice, including
MiaPaca, MDA-MB 231 and H-69, at doses between 1 and 20 mg/kg. To further explore the therapeutic potential of ISIS 2503,
a number of oligonucleotide/liposome formulations were prepared, and their abilities to increase both oligonucleotide in tumor tissue
as well as antitumor activity were evaluated in vivo. |
