Ludwig Institute for Cancer Research Limited

The University of Birmingham

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

Oxford University Innovation Ltd

Statens Serum Institut

Gurdyal S Besra

Vincenzo Cerundolo

Liam R Cox

Gerd J Ritter

Jay A Berzofsky

Richard R Schmidt

Masaki Terabe

Jessica J O'Konek

Petr Illarionov

Gopal Reddy

Rengarajan Balamurugan

Mariolina Salio

Jonathan Silk

Peter Andersen

Else Marie Agger

Claire Andersen

David E Minnikin

Petr A Illarionov

Disclosed herein are &#x3b1;-galactosylceramide (&#x3b1;-GalCer) analogs and compositions thereof, methods of activating invariant Natural Killer T (iNKT) cells using said analogs, methods of treating diseases by activating iNKT cells using said analogs, and combination therapy of said analogs.

iNKT cell modulators and methods of using the same

&#x3b2;-mannosylceramides or salts or solvates thereof in a pharmaceutically acceptable carrier, for use as a Type I NKT cell agonist in conjunction with a therapeutically effective amount of &#x3b1;-galactosylceramide or a salt or a solvate thereof, and/or at least one or more T-cell co-stimulatory molecules, disclosed. Compositions comprising &#x3b2;-mannosylceramide, as well as methods of treatment of tumors are also provided.

Beta-mannosylceramide and stimulation of NKT cell anti-tumor immunity

&#x3b2;-mannosylceramide and stimulation of NKT cell anti-tumor immunity

Here we identify MMG and its alpha- and ketomycolic acid derivatives as highly bioactive lipids derived fromBCG (Copenhagen) capable of stimulating and activating human DC's at exceedingly low doses. In addition to their direct role as immunostimulators of human DC's we demonstrate their use in the development of a new generation of adjuvants suitable for human administration. We furthermore identify a number of highly active synthetic MMG analogues with great potential in cancer treatment, and for vaccine adjuvants against both infectious disease and disorders like Alzheimers disease.

Use of monomycolyl glycerol (MMG) as an adjuvant

Analogs of alpha galactosylceramide and uses thereof

There are disclosed compound of formula I, in which Rrepresents a hydrophobic moiety adapted to occupy the C' channel of human CDId, Rrepresents a hydrophobic moiety adapted to occupy the A&#x2032; channel of human CDId, such that Rfills at least at least 30% of the occupied volume of the C&#x2032; channel compared to the volume occupied by the terminal nCHof the sphingosine chain of &#x3b1;-galactosylceramide when bound to human CDId and Rfills at least 30% of the occupied volume of the A&#x2032; channel compared to the volume occupied by the terminal nCHof the acyl chain of &#x3b1;-galactosylceramide when bound to human CDId Rrepresents hydrogen or OH, Rand Reach represent hydrogen and in addition, when Rrepresents hydrogen, Rand Rtogether may form a single bond, X represents or &#x2014;CHA(CHOH)Y or &#x2014;P(=0)(0)0CH(CH0H)Y, in which Y represents CHBB, n represents an integer from 1 to 4, m represents 0 or 1, A &#xe5;represents hydrogen, one of Band Brepresents H, OH or phenyl, and the other represents hydrogen or one of Band Brepresents hydroxyl and the other represents phenyl, in addition, when n represents 4, then A together with one of Band Btogether forms a single bond and the other of Band Brepresents H, OH or OSOH and pharmaceutically acceptable salts thereof; the compounds of formula I are indicted for use in the treatment of a virus, microbial infection, parasite, an autoimmune disease, cancer, allergy or asthma. 

Analogs of alpha galactosyceramide and uses thereof

Growing community of inventors

Birmingham, United Kingdom

Gurdyal S Besra