Sloan-kettering Institute for Cancer Research

Columbia University

Cornell Research Foundation Inc.

University of Kent

Jochen Buck

Koji Nakanishi

Fadila Derguini

Ulrich Hammerling

Karl Henry Nocka

Peter Besmer

Malcolm A Moore

Lorraine J Gudas

Alexander W Langston

Charles Achkar

Malcolm A S Moore

Urlich Hammerling

Felix Grun

Lonny R Levin

Fritz A Mühlschlegel

A pharmaceutical composition which comprises the c-kit ligand (KL) purified by applicants or produced by applicants' recombinant methods in combination with other hematopoietic factors and a pharmaceutically acceptable carrier is provided as well as methods of treating patients which comprise administering to the patient the pharmaceutical composition of this invention. This invention provides combination therapies using c-kit ligand (KL) and a purified c-kit ligand (KL) polypeptide, or a soluble fragment thereof and other hematopoietic factors. It also provides methods and compositions for ex-vivo use of KL alone or in combination therapy. A mutated KL antagonist is also described. Such an antagonist may also be a small molecule. Antisense nucleic acids to KL as therapeutics are also described. Lastly, compositions and methods are described that take advantage of the role of KL in germ cells, mast cells and melanocytes.

C-kit ligand-based method for expanding peripheral blood cell levels

Compositions comprising c-kit ligand, TNF-.alpha., and a hematopoietic factor are useful to promote the expansion of peripheral blood cells or the expansion and differentiation of hematopoietic progenitor cells.

Use of c-kit ligand with TNF-.alpha. and hematopoietic factors for the

Composition of c-kit ligand, GM-CSF, and TNF-.alpha. and method of use

For the first time, certain retinoids with a side chain terminal CH.sub.2 OH group or ester or ether thereof or aldehyde rather than a side chain terminal COOH group and substitution at the 4-position have been indicated to bind to nuclear receptors and to be biologically active in inducing cell differentiation of normal and tumor cells. These compounds activate gene expression through binding to nuclear receptor proteins. These compounds induce differentiation in normal and cancer cells and are useful for treating leukemias, and lymphomas, squamous cell carcinomas, deep (cystic) acne, psoriasis and photodamaged or aging skin. These compounds have stability and in vitro half-life advantages over and solubility differences from all-trans-retinoic acid and activity advantages over 13-cis retinoic acid.

Regulating gene expression using retinoids with CH.sub.2 OH or related

Method for increasing the level of stem cells in peripheral blood

The present invention relates to retinol dehydratase, the enzyme which synthesizes the retro-retinoid anhydroretinol in the Spodoptera frugiperda insect cell line Sf-21, as well as the DNA molecule encoding that enzyme. The DNA molecule can be incorporated in a DNA expression system and a host for recombinant production of anhydroretinol dehydratase. The isolated retinol dehydratase protein or polypeptide of the present invention can be combined with a pharmaceutically-acceptable carrier or used alone for administration to mammals, particularly humans, for preventing cell growth and/or uncontrolled cell growth in cells which are growth dependent on retinol and/or 14 hydroxy-4, 14-retro-retinol.

Isolation, purification and cloning of retinol dehydratase

Retinol derivatives useful for enhancing immune response

This invention provides methods of inhibiting the growth of cells, of treating a subject having a disease characterized by an uncontrolled growth of cells and of blocking an immune response as well as related inflammatory responses in a subject which comprises administering a compound having the structure: ##STR1##

Anhydroretinol and derivatives thereof as antagonists of immune

The present invention provides a purified retinoid compound characterized by a molecular mass of about 320 daltons and an atomic composition of C.sub.20 H.sub.32 O.sub.3. The present invention also provides a purified retinoid compound having the structure: ##STR1## wherein the configuration of the C7, C9, and C11 double bond independently is Z or E and the absolute configuration at C13 and C14 is independently R or S; wherein R1 is alkyl, alkyl halide, alcohol, ester, ether, aldehyde, ketone, carboxylic acid, carboxylic ester, acyl halide, amide, nitrile, or amine; R2 and R3 are independently hydroxyl, halide, alkoxy, ester, alkyl, alcohol, ether, aldehyde, ketone, carboxylic acid, carboxylic ester, nitrile, amine, azide, alkyl halide, acid halide, acid azide, or amide; or wherein R2 and R3, or R1 and R2 are replaced by a 13,14-oxirane or a 14,15-oxirane group, respectively.

Retinol derivatives and uses thereof

Regulating gene expression using retinoids with Ch.sub.2 OH or related

Compositions of soluble C-kit ligand and hematopoietic factors

This invention provides a homogeneous retro-retinoid compound, a method of enhancing the growth of a cell in a vitamin A reduced environment, a method for enhancing transcription of a gene regulated by retinoid in a cell, and a method for enhancing an immune response in a subject, wherein the compound has the structure: ##STR1##

Retro-alpha-retinol derivative and uses of retro-alpha-retinol

This invention provides a purified retro-retinoid compound characterized by a molecular mass of about 302 daltons. Also provided by this invention is a method of enhancing the growth of a cell in a vitamin A reduced environment which comprises contacting the cell with an effective growth enhancing amount of a compound having a structure: ##STR1## wherein the configuration of the C6, C8, C10 and C12 double bond independently is Z or E and the absolute configuration at C-14 is independently R or S; wherein R.sub.1 is alkyl, alkyl halide, alcohol, ester, ether, aldehyde, ketone, carboxylic acid, carboxylic ester, acid halide, amide, nitrile, or amine; and wherein R.sub.2 is hydroxyl, halide, alkoxy, ester, alkyl, alcohol, ether, aldehyde, ketone, carboxylic acid, carboxylic ester, nitrile, amine, azide, alkyl halide, acid halide, acid azide, or amide; or wherein R.sub.1 and R.sub.2 are replaced by a 14, 15-oxirane group; and wherein the retro structure is alpha or gamma. Further provided are a method for enhancing transcription of a gene regulated by retinoid in a cell, or a method for enhancing an immune response in a subject.

Retro-.alpha.-retinol (4,14-retro-retinol) derivatives and uses of

Growing community of inventors

New York, NY, United States of America

Jochen Buck