Imclone LLC

Other

Bronislaw Pytowski

Krishnadatt Persaud

Nathalie Zayek

Ihor R Lemischka

Kateri Moore

Larry Witte

The present invention provides anti-VEGFR-3 monoclonal antibodies, pharmaceutical compositions containing said antibodies and uses of said antibodies in the treatment of disease.

Anti-VEGFR-3 antibody compositions

Primitive hematopoietic stem cells are closely associated with discrete in vivo microenvironments. These &ldquo;niches&rdquo; are thought to provide the molecular signals that mediate stem cell differentiation and self renewal. We have dissected the fetal liver microenvironment into distinct cellular components by establishing an extensive panel of stromal cell lines. One particular cell line maintains repopulating stem cells for prolonged in vitro culture periods. A subtraction cloning strategy has yielded a cDNA which encodes a cell surface glycoprotein with a restricted pattern of expression among stromal cell lines. This molecule, previously identified as dlk/Pref-1, contains EGF-like repeats which are related to those in the Notch/Delta/Serrate family of proteins. We have investigated the potential role of this molecule in hematopoietic stem/progenitor cell regulation. We show that the dlk protein displays activity on purified stem cells by promoting the formation of &ldquo;cobblestone areas&rdquo; of proliferation. These cobblestone areas contain both primitive high-proliferative potential progenitors as well as in vivo repopulating stem cells.

Use of delta-like protein to inhibit the differentiation of stem cells

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New York, NY, United States of America

Bronislaw Pytowski