Targeting of AML-leukemic SC with monoclonal antibodies

Targeting of AML-leukemic stem cells with monoclonal antibodies by Erwin M Lee‌ and Richard B Lock, Future Oncol 2009(Nov); 5(9): 1327-30 [PubMed Citation][FriendFeed entry][Full text PDF]. Final sentence of the full text of this Editorial:

An AML patient surface immunophenotype is relatively cost-effective to characterize, raising the prospect of individualized therapy based on a selection of available MAbs. Most certainly, we are entering a new and exciting era in the struggle to improve outcome in adult AML.

Antitumor activity of anti-DLL4 antibodies

Data Published in Cell Stem Cell Demonstrates Potent Anti-Cancer Activity for OncoMed Pharmaceuticals Lead Antibody, Health Informer, August 7, 2009. Subtitle: Targeting Cancer Stem Cells Dramatically Reduces Tumor Growth and Recurrence in Preclinical Models. First paragraph:

OncoMed Pharmaceuticals, Inc. announced the publication in Cell Stem Cell of data demonstrating potent anti-cancer activity in colon and breast cancer models for the company’s first product candidate, OMP-21M18, underlining the therapeutic potential of targeting cancer stem cells to treat solid tumors. OMP-21M18 is currently in Phase 1 clinical testing.

The publication: DLL4 Blockade Inhibits Tumor Growth and Reduces Tumor-Initiating Cell Frequency by Timothy Hoey and 14 co-authors, including Michael F Clarke, John Lewicki and Austin Gurney, Cell Stem Cell 2009(Aug 7); 5(2): 168-77. [PubMed Citation][FriendFeed entry].[Full text of this "Featured Article", via Gratis OA][Full text PDF].

Examples of other links to the News Release: [OncoMed.com (PDF)][Medical News Today][Genetic Engineering & Biotechnology News].

Leukemia SC cloak themselves to avoid detection

Leukemia cells evade immune system by mimicking normal cells, Stanford study shows by Krista Conger, News Release, Stanford University Medical Center, July 23, 2009. First sentence:

Human leukemia stem cells escape detection by co-opting a protective molecular badge used by normal blood stem cells to migrate safely within the body, according to a pair of studies by researchers at Stanford University Medical School.

See also: Molecule Helps Leukemia Cells Hide From Immune System, Drugs.com, July 23, 2009. First sentence:

Leukemia stem cells cleverly cloak themselves to avoid detection by a person's immune system, according to a pair of studies by researchers at Stanford University Medical School.

And: Leukemia cells evade immune system by mimicking normal cells, Stanford studies show, EurekAlert, July 23, 2009.

The two articles upon which the news releases are based:

1) CD47 Is Upregulated on Circulating Hematopoietic Stem Cells and Leukemia Cells to Avoid Phagocytosis by Siddhartha Jaiswal, Catriona H M Jamieson and 7 co-authors, including Irving L Weissman, Cell 2009(Jul 23); 138(2): 271-85. [PubMed Citation].

2) CD47 Is an Adverse Prognostic Factor and Therapeutic Antibody Target on Human Acute Myeloid Leukemia Stem Cells by Ravindra Majeti and 7 co-authors, including Irving L Weissman, Cell 2009(Jul 23); 138(2): 286-99. [PubMed Citation][FriendFeed entry].

Targeted therapy for AML stem cells

New Targeted Therapy Finds And Eliminates Deadly Leukemia Stem Cells, ScienceDaily July 3, 2009. [FriendFeed entry]. First paragraph:

New research describes a molecular tool that shows great promise as a therapeutic for human acute myeloid leukemia (AML), a notoriously treatment-resistant blood cancer. The study, published in the July 2nd issue of the journal Cell Stem Cell, describes exciting preclinical studies in which a new therapeutic approach selectively attacks human cancer cells grown in the lab and in animal models of leukemia.

The news release is about this article: Monoclonal antibody-mediated targeting of CD123, IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells by Liqing Jin and 14 co-authors, including John E Dick and Richard B Lock, Cell Stem Cell 2009(Jul 2); 5(1): 31-42. [PubMed Citation].

Therapeutic monoclonal antibody targeting of AML-LSCs

New Targeted Therapy Finds And Eliminates Deadly Leukemia Stem Cells, ScienceDaily July 3, 2009. [FriendFeed entry]. First two sentences:

New research describes a molecular tool that shows great promise as a therapeutic for human acute myeloid leukemia (AML), a notoriously treatment-resistant blood cancer. The study, published in the July 2nd issue of the journal Cell Stem Cell, describes exciting preclinical studies in which a new therapeutic approach selectively attacks human cancer cells grown in the lab and in animal models of leukemia.

This news release is about the article Monoclonal antibody-mediated targeting of CD123, IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells by Liqing Jin and 14 co-authors, including John E Dick and Richard B Lock, Cell Stem Cell 2009(Jul 2); 5(1): 31-42. PubMed Abstract:

Leukemia stem cells (LSCs) initiate and sustain the acute myeloid leukemia (AML) clonal hierarchy and possess biological properties rendering them resistant to conventional chemotherapy. The poor survival of AML patients raises expectations that LSC-targeted therapies might achieve durable remissions. We report that an anti-interleukin-3 (IL-3) receptor alpha chain (CD123)-neutralizing antibody (7G3) targeted AML-LSCs, impairing homing to bone marrow (BM) and activating innate immunity of nonobese diabetic/severe-combined immunodeficient (NOD/SCID) mice. 7G3 treatment profoundly reduced AML-LSC engraftment and improved mouse survival. Mice with pre-established disease showed reduced AML burden in the BM and periphery and impaired secondary transplantation upon treatment, establishing that AML-LSCs were directly targeted. 7G3 inhibited IL-3-mediated intracellular signaling of isolated AML CD34(+)CD38(-) cells in vitro and reduced their survival. These results provide clear validation for therapeutic monoclonal antibody (mAb) targeting of AML-LSCs and for translation of in vivo preclinical research findings toward a clinical application.