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

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...

AI Technical Summary

Benefits of technology

[0027]In one embodiment, the present invention provides methods of inhibiting the proliferation of HTCs of myeloid origin by contacting the HTCs with a composition comprising an antibody or other agent directed to one or more of the disclosed members of the Ig superfamily or TLR superfamily. In another embodiment, the present invention provides methods of mediating the destruction of HTCs of myeloid origin by contacting the HTCs with a composition comprising an antibody or other agent directed to one or more of the disclosed members of the Ig superfamily or TLR superfamily. In one embodiment, the antibody is a monoclonal antibody that specifically binds an epitope on a disclosed member of the Ig superfamily or TLR superfamily or a portion thereof. In another embodiment, the composition comprises an antibody complex.

[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 disclosed members of the Ig superfamily or TLR superfamily is detected and wherein the expression product level is correlated with a treatment outcome. In one embodiment, the expression product is RNA and lower expression levels correlate with more favorable outcomes.

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 and mortality.

This therapeutic approach has limited application because of its dependence on the availability of suitable donors and because the treatments show better outcome for patients in the chronic or early phase of the disease as compared to acute or late stages.

Because antibody therapy targets cells expressing a particular antigen, there is a possibility of cross-reactivity with normal cells and can lead to detrimental results.

Immunotherapy as a treatment option against hematpoietic cancers, such as AML, is limited by the lack of tumor-associated antigens that are tumor-specific and that are shared among diverse patients.

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