Folate targeting: remarkable antitumor activity-100% tumor-free animals
 

<dl class="AbstractPlusReport"><dt class="head">Cancer Res. 2008 Dec 1;68(23):9839-44.
</dt><dd class="abstract"> Folate targeting enables durable and specific antitumor responses from a therapeutically null tubulysin B analogue.

<!--AuthorList-->Leamon CP, Reddy JA, Vetzel M, Dorton R, Westrick E, Parker N, Wang Y, Vlahov I.
Endocyte, Inc., West Lafayette, Indiana.
The membrane-bound high-affinity folate receptor (FR) is highly expressed on a wide range of primary and metastatic human cancers,we explored the possibility of using the folate ligand to target a potent, semisynthetic analogue of the microtubule inhibitor tubulysin B to FR-enriched tumors. such as those originating in ovary, lung, breast, endometrium, kidney, and brain. Because folate-linked conjugates bind to and become internalized within FR-expressing cells (similar to that of free folic acid), When tested in vitro, a novel folate conjugate, herein referred to as EC0305, was found to specifically inhibit the growth of a panel of FR-positive cell lines (IC(50) range, 1-10 nmol/L) in a dose-dependent manner, whereas cells lacking FR expression were unaffected. The potency of EC0305 was also confirmed against a human KB xenograft-nu/nu mouse cancer model. Here, a brief three times per week, 2-week regimen yielded remarkable antitumor activity (100% tumor-free animals) without causing significant weight loss or major organ tissue degeneration. In contrast, antitumor activity was completely abolished in EC0305-treated animals that were co-dosed with an excess of a nontoxic folate-containing analogue, thereby confirming that the antitumor effect of this agent was mediated by FRs. The advantage provided by folate conjugation was further proved by the untargeted free drug, which was found to be completely inactive at both tolerable and highly toxic dose levels. Collectively, these results show that this potent antiproliferative tubulysin compound can be specifically delivered to FR-positive tumors to provide substantial therapeutic benefit using well-tolerable dosing regimens. [Cancer Res 2008;68(23):9839-44].</dd></dl>http://www.endocyte.com/technology.html

"Our lead program uses the vitamin folate to target cancer cells. Folate is required for cell division and rapidly dividing cancer cells over-express a receptor for folate. By attaching drugs to folate, we are able to target drugs directly at cancer cells with less potential toxicity to surrounding healthy cells."


A related (folate targeting) phase 1 study for solid tumors:
http://www.clinicaltrials.gov/ct2/sh...ndocyte&rank=1

Re: Folate targeting: remarkable antitumor activity-100% tumor-free animals
 

.................................................. .............................

Re: Folate targeting: remarkable antitumor activity-100% tumor-free animals
 

Interesting.