Immunoglobulin and/or Toll-Like Receptor Proteins Associated with Myelogenous Haematological Proliferative Disorders and Uses Thereof

a technology of immunoglobulin and toll-like receptors, which is applied in the direction of immunoglobulins against animals/humans, drug compositions, peptides, etc., can solve the problems of serious side effects, cytogenetic defects may not be solely responsible for proliferative traits, and toxicity to dividing cells, so as to achieve favorable outcomes and lower expression levels

Inactive Publication Date: 2011-02-24
CELLERANT THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0031]In another embodiment, the present invention provides prognostic methods for predicting the efficacy of treating a haematological proliferative disorder of myeloid origin, where the level of an expression product corresponding to one or more of the dis...

Problems solved by technology

Although myeloproliferative disorders, such as AML and CML are typically associated with cytogenetic abnormalities, the cytogenetic defect may not be solely responsible for the proliferative trait.
For instance, busulfan, a bifunctional alkylating agent, and hydroxyurea, an inhibitor of ribonucleoside diphosphate, affect DNA synthesis and stability, resulting in toxicity to dividing cells.
However, the effects of these agents are non-discriminatory and as a result they have serious side effects due to toxicity to normal dividing cells.
Transplant with less well matched donors marketed increases the transplant related morbidity...

Method used

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  • Immunoglobulin and/or Toll-Like Receptor Proteins Associated with Myelogenous Haematological Proliferative Disorders and Uses Thereof
  • Immunoglobulin and/or Toll-Like Receptor Proteins Associated with Myelogenous Haematological Proliferative Disorders and Uses Thereof
  • Immunoglobulin and/or Toll-Like Receptor Proteins Associated with Myelogenous Haematological Proliferative Disorders and Uses Thereof

Examples

Experimental program
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Effect test

example 1

10.1 Example 1

Identification of Members of the Immunoglobulin (Ig) Superfamily or Toll-Like Receptor (TLR) Superfamily Associated with HTCs

[0215]HTC markers were identified by comparing RNA transcript levels in normal HSCs and in AML CSCs for a variety of genes using microarrays. Specifically, data was obtained for test samples comprising AML Lin−CD34+CD38− cells, where three AML samples were taken from peripheral blood; Lin−CD34+CD38− and Lin−CD34+CD38+ cells were double sorted. The sorting strategy produced cells which were also over 90% CD90−. The sorting strategy produced purities greater than 98%.

[0216]To allow for direct comparison, data was then obtained from control samples comprising normal HSCs. A sample was taken from mobilized peripheral blood (MPB) of each of three individual donors and Lin−CD34+CD90+CD45RA−CD38− and Lin− CD34+CD90+CD45RA−CD38+ cells were double sorted. The sorting strategy produced a purity of over 99%.

[0217]For both sorting strategies, the Lineage (Li...

example 2

10.2 Example 2

Production and In Vivo Efficacy of Monoclonal Antibodies

10.2.1. Preparation of Monoclonal Antibodies that Specifically Bind a Member of the Immunoglobulin (Ig) Superfamily or Toll-Like Receptor (TLR) Superfamily Associated with HTCs

[0224]Techniques for producing the monoclonal antibodies are known in the art and are described, for instance, in Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103 (Academic Press, 1986). Immunogens that may be employed include a purified polypeptide corresponding to CD84; lymphocyte antigen 86 (Ly86); CD180 (RP105); HAVCR2; LILRA1; LILRA2, NEGR1; or TLR2, as well as fusion proteins containing the same. Alternatively, cells expressing recombinant an AML-expressed isoform of CD84; Ly86; CD180; HAVCR2; LILRA1; LILRA2, NEGR1; or TLR2, on the cell surface, may be used. Selection of the immunogen can be made by the skilled artisan without undue experimentation.

[0225]Mice, such as Balb / c, are immunized with the selected immunogen,...

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Abstract

The disclosure relates to methods and compositions effective in the diagnosis, prognosis and treatment of human hematopoietic cancers. In particular, the disclosure provides tumor-associated genes that encode for members of the immunoglobulin (Ig) and/or toll-like receptor superfamilies that are differentially expressed in hematopoietic tumor cells of myeloid origin compared with other cells, e.g., normal stem cells.

Description

[0001]This application claims the benefit of priority under 35 U.S.C. §119 of U.S. application Ser. No. 61 / 039,701 (filed Mar. 26, 2008), which is incorporated herein by reference in its entirety.1. TECHNICAL FIELD[0002]The present disclosure relates generally to agents capable of specifically targeting cancer stem cell markers and methods of using the agents, particularly in diagnostic and therapeutic treatments. In particular, the present disclosure provides proteins belonging to the immunoglobulin (Ig) superfamily or the toll-like receptor (TLR) superfamily as novel cancer stem cell targets that are expressed extracellularly and that are targeted by antibodies and other agents disclosed herein.2. BACKGROUND[0003]The cells of the hematopoietic system arise from multipotent progenitors, the hematopoietic stem cells (HSCs), which progress through a series of developmental programs to ultimately form the terminally differentiated cells of the myeloid or lymphoid lineage. It is believ...

Claims

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Application Information

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IPC IPC(8): A61K51/00C07K16/28C07K16/18A61K39/395C12N5/09C40B30/00C12Q1/68A61P35/00A61P35/02
CPCG01N2800/52Y10T436/143333A61K45/06C07K16/28G01N33/57426G01N33/56966G01N2333/726C07K16/2866A61K2039/505C07K2317/73A61K39/39558A61P35/00A61P35/02
Inventor KARSUNKY, HOLGER
Owner CELLERANT THERAPEUTICS INC
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