US Patent 7632678 about CSC

Cancer stem cells and uses thereof, United States Patent 7632678. Issued on December 15, 2009. (Filing Date was November 22, 2006).

Inventors: Loen M Hansford, Kristen M Smith, Alessandro Datti, Freda M Miller and David R Kaplan (Toronto, Canada).

Assignee: The Hospital for Sick Children (Toronto, Ontario, Canada).

Abstract:

Disclosed are enriched preparations of neuroblastoma tumor initiating cells (NB TICs). The NB TICs are capable of self-renewal, initiating neuroblastoma tumor growth in vivo and are capable of being passaged in high frequency. These NB TICs have chromosomal abnormalities and are capable of giving rise to secondary tumor spheres. Methods are also disclosed for preparing the enriched preparations of NB TICs, such as from neuroblastoma tumor tissue and metastasized bone marrow. Also disclosed are methods of screening candidate substances to identify therapeutic agents for the treatment of neuroblastoma. Methods are also provided for screening a sample for neuroblastoma, as well as for screening a sample to identify the stage of neuroblastoma present. Kits are also provided for selecting appropriate anti-neuroblastoma compounds for a patient, and utilize isolated compositions of the patients' neuroblastoma tumor initiating cells. In this manner, a customized medicinal profile for the patient may be devised.

Targeting tumorogenic cells in neuroblastoma cell lines

Neuroblastoma Cell Lines Contain Pluripotent Tumor Initiating Cells That Are Susceptible to a Targeted Oncolytic Virus by Yonatan Y Mahller and 8 co-authors, including Timothy P Cripe, PLoS ONE 2009; 4(1): e4235 [Epub 2009 Jan 21]. [The full text is openly accessible]. PubMed Abstract:

BACKGROUND: Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers. METHODOLOGY/PRINCIPAL FINDINGS: Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice. CONCLUSIONS/SIGNIFICANCE: These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.

Examples of news items about this publication:

Targeting Cancer's Own Stem Cells to Fight Recurrence, Forbes, January 21, 2009. First paragraph:

Scientists have located a group of cancer stem cells or "tumor-initiating cells" which, when targeted with a reprogrammed herpes virus, are prevented from turning malignant.

Engineered Virus Targets And Kills Apparent Cancer Stem Cells In Neuroblastoma, ScienceDaily, January 21, 2009. First paragraph:

After identifying an apparent population of cancer stem cells for neuroblastoma, researchers successfully used a reprogrammed herpes virus to block tumor formation in mice by targeting and killing the cells.

Virus made to kill cancer stem cells, UPI, January 22, 2009. First paragraph:

U.S. scientists say they have engineered a virus to target and kill apparent cancer stem cells involved in neuroblastoma tumors.