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O-methylated rapamycin derivatives for alleviation and inhibition of lymphoproliferative disorders

a technology of rapamycin and derivatives, which is applied in the field of omethylated rapamycin derivatives for alleviating and inhibiting lymphoproliferative disorders, can solve the problems of malignant lymphoma type ptlds, the ineffective modification of conventional treatment with conventional agents, and the ability of the body, so as to alleviate the disorder, alleviate the disorder, and alleviate the effect of lymphoproliferative disorders

Inactive Publication Date: 2008-07-31
THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The invention is about a method of treating lymphoproliferative disorders in humans using a rapamycin derivative. The method can alleviate or prevent the disorder and can be used in combination with other pharmacologically active agents like immunosuppressive agents. The method can also be used to assess the effectiveness of an agent for treating lymphoproliferative disorders in mammals. The technical effect of the invention is to provide a novel method for treating lymphoproliferative disorders that targets the underlying cause of the disorder and reduces the risk of graft rejection or metastasis of lymphatic tumors."

Problems solved by technology

However, lowering the dose of standard immunosuppressive drugs, which nullify the body's ability to reject and destroy foreign tissue, can jeopardize the survival of a graft.
Moreover, this modification in treatment with conventional agents is not effective against malignant, lymphoma-type PTLDs which are usually fatal for the graft recipient.
Low grade lymphomas are usually slowly progressive, but are essentially non-curable.
These aggressive types of lymphoma result in a rapid demise of the patients who do not respond to therapy.
Prognosis of lymphomas occurring in patients who are immunocompromised such as AIDS and post-transplant patients, is particularly poor.

Method used

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  • O-methylated rapamycin derivatives for alleviation and inhibition of lymphoproliferative disorders
  • O-methylated rapamycin derivatives for alleviation and inhibition of lymphoproliferative disorders
  • O-methylated rapamycin derivatives for alleviation and inhibition of lymphoproliferative disorders

Examples

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example 1

SDZ RAD Inhibits Growth of Human EBV-Transformed B Lymphocytes In Vitro and In Vivo

[0101] The experiments presented in this Example demonstrate that SDZ RAD is a potent anti-rejection, anti-lymphoproliferative agent, and represents a novel approach to inhibition and treatment of post-transplant lymphoproliferative disorders (PTLDs).

[0102] The materials and methods used in the experiments presented in this Example are now described.

[0103] Most cell lines used in this study were lymphoblastoid B-cell lines obtained by in vitro infection with EBV of peripheral blood mononuclear cells (PBMC). Cell lines A1 and A2D6 were obtained from normal, healthy individuals. Cell lines 15A and 20A were obtained from two different patients with a low grade B-cell lymphoma with monoclonal cold agglutinins (Silberstein et al., 1991, Blood 78:2372-2386). Both lines secreted cold agglutinins with the same specificity as the cold agglutinins found in the patient's serum (Silberstein et al., 1991, Blood...

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Abstract

The present invention relates to methods of alleviating and inhibiting a lymphoproliferative disorder in a mammal, the method comprising administering one or more rapamycin derivatives (including rapamycin) to the mammal. Further, the invention provides a method for identifying agents which are useful for alleviating and inhibiting a lymphoproliferative disorders, as well as a method for identifying agents which are capable of inhibiting metastasis of lymphatic tumors in a mammal.

Description

BACKGROUND OF THE INVENTION [0001] Post-transplant lymphoproliferative disorders (PTLDs) which usually involve expansion of B lymphocytes infected with the Epstein-Barr virus (EBV), are a life-threatening complication of the immunosupressive therapy necessary to inhibit graft rejection (Morrison et al., 1994, Am. J. Med. 97:14-24; Warnke et al., 1995, AFIP Fascicle 14:531-535). PTLDs comprise a whole spectrum of lymphoproliferative disorders ranging from a polyclonal atypical lymphoid hyperplasia to a monoclonal, overtly malignant B-cell lymphoma (Morrison et al., 1994, Am. J. Med. 97:14-24; Warnke et al., 1995, AFIP Fascicle 14:531-535; Curtis et al., 1999, Blood 94:2208-2216; Harris et al., 1997, Semin. Diagn. Path. 14:8-14). Less advanced forms of PTLDs respond to a less aggressive course of immunosuppressive therapy (Morrison et al., 1994, Am. J. Med. 97:14-24; Sigal et al., 1992, Ann. Rev. Immunol. 10:519-60). However, lowering the dose of standard immunosuppressive drugs, whic...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/4745A61K31/343C07D498/18A61K31/42A61K31/436A61K31/44A61K31/445A61K31/52A61K31/664A61K33/24A61K38/00A61K39/395A61K45/00A61P35/00A61P35/02A61P37/06G01N33/50
CPCA61K31/436A61K31/44A61K31/445A61K31/4745G01N33/5011G01N33/5052A61K2300/00A61P31/22A61P35/00A61P35/02A61P35/04A61P37/06A61P43/00
Inventor WASIK, MARIUSZ A.SHAW, LESLIE M.
Owner THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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