The United States of America, As Represented by the Secretary, Department of Health and Human Services

The United States of America As Represented by the Department of Health

University of Minnesota

Chiron Corporation

The Government of the United States of America, As Represented by the

Robert H Wiltrout

Ronald L Hornung

Bruce Robert Blazar

William J Murphy

Francis W Ruscetti

Jonathan R Keller

Susan Wilson

Kristin L Komschlies-McConville

Krzysztof Grzegorzewski

Phillipe Briet

Jean-Jacques Berthelon

Ronald Hornung

Francois Collonges

The invention provides a method of treating or preventing a pathologic state in a mammal. The method comprises administering to the mammal a promoter of T-cell expansion and an inducer of CD40 stimulation, wherein CD40 is stimulated on cells of the immune system. The promoter of T-cell expansion and inducer of CD40 stimulation are administered in synergistically effective amounts to treat or prevent the pathologic state in the mammal. The invention also provides a method of assessing the effectiveness of treatment of a pathologic state in a mammal, wherein the mammal has been administered a promoter of T-cell expansion and an inducer of CD40 stimulation, wherein CD40 is stimulated on cells of the immune system. The method comprises measuring the level of at least one antibody in a test sample obtained from the mammal, which at least one antibody is specific for an antigen that is known to be associated with the pathologic state, and wherein the level of the at least one antibody is indicative of the effectiveness of treatment of the pathologic state in the mammal.

Use of a promoter of T-cell expansion and an inducer of CD40 stimulation in the treatment or prevention of a pathologic state

This invention provides a method of isolating an increased number of hematopoietic stem cells from a subject comprising a) administering interleukin-7 to the subject in an amount that mobilizes the hematopoietic stem cells to the peripheral blood; and, b) isolating a population of leukocytes enriched for hematopoietic stem cells from the peripheral blood. Also provided is a method of transplanting an increased number of hematopoietic stem cells from a donor to a recipient to enhance repopulation of the recipient's hematopoietic and immune cells comprising a) administering interleukin-7 to the donor in an amount that mobilizes the hematopoietic stem cells to the peripheral blood; b) isolating a population of leukocytes enriched for hematopoietic stem cells from the donor's peripheral blood; and, c) transplanting the isolated population of leukocytes enriched for hematopoietic stem cells to the recipient, thereby enhancing the repopulation of the recipient's hematopoietic and immune cells. Finally, the invention provides a method of improving engraftment of a bone marrow transplant or a peripheral blood leukocyte transplant from a donor to a recipient comprising administering interleukin-7 to the recipient following transplantation in an amount that enhances engraftment.

Method of mobilizing pluripotential hematopoietic stem cells with IL-7

The use of substituted flavonoid compounds which have the immunomodulatory activity of (1) boosting natural killer activity in vivo and (2) inducing interferon, and (3) belong to the family of flavonoids of the formula (I): ##STR1## in conjunction with interleukin-2 in cancer therapy is disclosed.

Substituted flavonoid compounds, their salts, their manufacture and

The present invention relates to a method for protecting hematopoietic stem cells from the myelotoxicity of chemotherapeutic drugs or radiation therapy, which comprises, administering to a subject a therapeutically effective amount of transforming growth factor beta 1 for protecting bone marrow from the myelotoxicity of chemotherapeutic drugs or radiation therapy. The TGF.beta.1 may be administered prior (e.g. 24 hours) to the administration of the chemotherapeutic drugs or radiation therapy. Preferably, the TGF.beta.1 is administered to the subject in an amount of about 5 .mu.g to 25 .mu.g per kg body weight. The patient or subject of the present invention may be a mammal (e.g. human, domestic animal such as horse, cow, dog, cat or pig) and is preferably a human being. The mode of administration is either by interfemoral arterial, interperitoneally or subcutaneously, and preferably is by injection.

Method for protecting bone marrow against chemotherapeutic drugs using

Treatment of Cancer with Flavones and Interleukin 2.

Cancer therapy using interleukin-2 and flavone compounds

A treatment regimen for cancers having cells which are susceptible to an interleukin-2 activated natural killer cell mediated anti-cancer effect, the method comprises administering to a patient an effective amount of a combination of interleukin 2 and flavone-8-acetic acid. The treatment regimen is particularly effective in the treatment of renal carcinoma. Synergistic pharmaceutical compositions are also provided. effective in the treatment of renal carcinoma. Synergistic pharmaceutical compositions are also provided.

Flavone-8-acetic acid and interleukin-2 in a method of treating certain

A treatment regimen for cancer comprises administering to a patient an effective amount of a combination of interleukin 2 and flavone-8-acetic acid. The treatment regime is particularly effective in the treatment of renal cracinoma.

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Frederick, MD, United States of America

Robert H Wiltrout