CRLX101 is an experimental approach to

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

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 A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

, namely a cyclodextrin-based

polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...

(CDP) and an anti-cancer compound ( camptothecin). It was developed by Mark E. Davis, 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 founde ...

, 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 Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

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 Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

was conducted at the City of Hope National Medical Center, the

Translational Genomics Research Institute The Translational Genomics Research Institute (TGen) is a non-profit genomics research institute based in Arizona, United States. History and activities TGen was established in 2002 by Jeffrey Trent in Phoenix, Arizona, United States. T ...

, 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