Dendreon

Dendreon Pharmaceuticals LLC is a biotechnology company. Its lead product, Provenge (known generically as sipuleucel-T), is an immunotherapy for prostate cancer. It consists of a mixture of the patient's own blood cells (autologous, with dendritic cells thought to be the most important) that have been incubated with the Dendreon PAP-GM-CSF fusion protein. Phase III clinical trial results demonstrating a survival benefit for prostate cancer patients receiving the drug were presented at the AUA meeting on April 28, 2009.[1] After going through the approval process, Provenge was given full approval by the FDA on April 29, 2010.[2] Dendreon's stock value fell 66% on August 4, 2011, after abandoning its forecast for its debut drug Provenge.[3]

In November 2014, Dendreon filed for Chapter 11 bankruptcy protection and shortly afterwards announced that it had reached agreements on the terms of a financial restructuring with certain bond holders.[4]

Technology overview and pipeline

Antigen delivery cassette and antigen presenting cells

Dendreon's name derives from the "Dendritic Cell" which forms a major component of the company's product candidates that use the "Dendreon Cassette Technology" to insert a disease-specific target protein into a general platform. Their lead product, Provenge, is an example of their "rationally designed therapeutic process" intended to break immune tolerance to certain disease specific proteins. It is hypothesized that receptor mediated uptake of antigen by dendritic cells occurs when they are exposed to the Dendreon fusion protein which links the disease specific protein to a recognition protein. This approach is in contrast to other dendritic cell vaccines that use methods such as electroporation to get the DC's to present antigen related epitopes. In the case of Provenge, this disease related protein is prostatic acid phosphatase and the signalling component is GM-CSF.

Antigen selection

Dendreon believes its process can be optimized and generalized to other diseases by exchanging the PAP component of Provenge with better targets specific to different diseased cells.[7] Antigen selection is a significant issue with cancer vaccines in general. Presumably, therapeutic effect can be obtained by provoking a selective response against the diseased cells only. Dendreon has explored approaches to obtaining tumour-specific antigen targets under the theory that the immune system may be able to mount a more effective response than is otherwise possible against tumor associated antigens. Unaltered human PAP is expressed by normal prostate cells but recent discoveries suggest that cancer cells produce many more unique targets as well as proteins that are more highly expressed than in normal tissue.[8] It has also been recently discovered that other enzymes expressed in nerves are identical to PAP[9][10] and there is ongoing work to examine post-translational modifications to PAP and its correlation to disease state by Dendreon collaborators.[11] PAP also appears to be expressed in breast cysts.[12]

Prior work in this area has also included that of A. Sette at Epimmune and the Altered Peptide Ligand approach typified by Neurocrine Biotech's failed MS drug.

Nuvelo and patents acquired from Corvas

Dendreon acquired the nematode anticoagulant Nuvelo.[13] Selected Corvas patents include technologies for peptide analog synthesis and drugs that target coagulation and immune processes.

type	Private
founder	William A. Haseltine Edgar Engleman Samuel Strober
location city	Seal Beach, California
location country	U.S.
industry	Biomedicine
products	Provenge
services	Provenge
num employees	650
parent	Sanpower Group, Nanjing, CN
homepage	dendreon.com

Technology overview and pipeline

Antigen delivery cassette and antigen presenting cells

Antigen selection

Nuvelo and patents acquired from Corvas

Early history

Provenge

Dendreonites

External links

References