IT-101

IT-101 is a novel approach to cancer chemotherapy that is currently under investigation in human trials.

The agent represents a nano-particle conjugate that consists of a drug delivery molecule, namely a cyclodextrin-based polymer (CDP) (Cyclosert) and an anti-cancer compound (camptothecin). It was developed by Dr. Mark Davis and associates at Insert Therapeutics (now Calando Pharmaceuticals), hence the IT label. Its novel delivery mode allows the agent and thus the toxic anti-cancer component to be preferentially accumulated in cancer tissue. In turn, toxic side effect are expected to be reduced.

Rationale

Camptothecin (CPT), an alkaloid extract from plants such as Camptotheca acuminata, exhibits anti-cancer activity possibly due, at least in part, by the inhibition of DNA topoisomerase I resulting in cell death. CPT is linked covalently through a glycine link to CDP which in turn consists of beta-cyclodextrin and polyethylene-glycol (PEG). The compound is water soluble. After intravenous injection, CPT is slowly released as the linkage is hydrolysed. The size of the compound facilitates its extravasation in the more leaky vessels of a cancer and the anticancer drug is retained in the abnormal tissue. As such the chemotherapeutic effect is enhanced in tumor tissue.

Phase I study

The Phase I clinical trial is conducted at the City of Hope Cancer Center. Patients who were entered had refractory and resistant solid tumor cancer of various types (pancreatic cancer, ovarian cancer, non small cell lung cancer). The initial study recruited 36 patients, beginning in May 2006, and is estimated to last until January 2008. Treatment consists of injections on day 1, 8, and 15 followed by 1 week rest.

Animal studies

The agent was studied in mouse xenografts using different cancer models and showed good tolerability and anti-cancer effectiveness in a variety of tumors. [Schluep T, Hwang J, Cheng J, Heidel JD, Bartlett DW, Hollister B, Davis ME. Preclinical efficacy of the camptothecin-polymer conjugate IT-101 in multiple cancer models. Clin. Cancer Res.2006 Mar 1;12(5):1606-14. ] [Cheng J, Khin KT, Davis ME. Antitumor activity of beta-cyclodextrin polymer-camptothecin conjugates. Mol.Pharm. 2004 May-Jun;1(3):183-93. ]

References

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* [http://clinicaltrials.gov/ct/show/NCT00333502?order=1 Phase I study Protocol] Study of IT-101 in the Treatment of Advanced Solid Tumors

External links

* [http://www.insertt.com/ Insert Therapeutics website]
* [http://www.thirteen.org/curious/episodes/qa-mark-davis/ Q&A with Mark Davis on Thirteen]