CRLX101 is an experimental approach to cancer chemotherapy that is under investigation in human trials. It is an example of a nanomedicine. The agent represents a nanoparticle conjugate that consists of a drug delivery molecule, namely a cyclodextrin-based polymer (CDP) and an anti-cancer compound ( camptothecin). It was developed by

Mark E. Davis Mark E. Davis is the Warren and Katherine Schlinger Professor of Chemical Engineering at the California Institute of Technology. He is a member of the City of Hope National Medical Center. He earned his B.S., M.S., and Ph.D. in chemical en ...

, professor of Chemical Engineering at the California Institute of Technology, and associates at

Insert Therapeutics Insert Therapeutics, Inc., now Calando Pharmaceuticals, Inc., is a medical research company that uses nanobiotechnology specializing in therapeutic agents that are conjugated, to facilitate and enhance drug delivery. The small company was founded ...

, Inc., now Calando Pharmaceuticals, Inc., hence the original name "IT-101". 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. The technology was licensed by Calando and Caltech to Cerulean Pharma, in 2009.

Rationale

Camptothecin (CPT), an alkaloid extract with poor water solubility from plants such as '' Camptotheca acuminata'', exhibits anti-cancer activity possibly due, at least in part, by the inhibition of DNA

topoisomerase DNA topoisomerases (or topoisomerases) are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues i ...

I resulting in cell death. In CRLX101, CPT is linked covalently through a glycine link to the linear copolymer CDP, which in turn consists of alternating subunits of beta- cyclodextrin and polyethylene glycol (PEG). The CRLX101 nanoparticle is water-soluble. After intravenous injection, active CPT is slowly released as the linkage is hydrolyzed. The size of the nanoparticle (20-50 nm in diameter) facilitates its extravasation in the more leaky vessels of tumors via the enhanced permeability and retention effect and as a result, the anticancer drug is enhanced and retained in the tumor tissue.

Clinical trials

The Phase 1/2a clinical trial was conducted at the City of Hope National Medical Center, the Translational Genomics Research Institute, and San Juan Oncology Associates.

Alternate drug name

CRLX101 was originally named IT-101 and was changed to CRLX101 after licensing to Cerulean Pharma Inc. CRLX101 is the official name in clinical trials.

Media

IT-101 and Mark E. Davis were included in a PBS documentary titled ''Survival''.{{cite web , url = http://www.thirteen.org/curious/survival/watch-the-full-episode-survival/23/ , title = ''Survival'' , website = thirteen.org

References

External links

Calando Pharmaceuticals, Inc.
was Insert Therapeutics, Inc.
Cerulean Pharma Inc.
CRLX101 licensee and current developer
Q&A with Mark Davis on Thirteen

at California Institute of Technology Experimental cancer drugs