The present invention provides compositions and methods for inhibiting one or more diacylglycerol kinase (DGK) isoform in a cell in order to enhance the cytolytic activity of the cell. In one embodiment, the cells may be used in adoptive T cell transfer. For example, in some embodiments, the cell is modified to express a chimeric antigen receptor (CAR). Inhibition of DGK in T cells used in adoptive T cell transfer increases cytolytic activity of the T cells and thus may be used in the treatment of a variety of conditions, including cancer, infection, and immune disorders.

THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

The Trustees of the University of Pennsylvania

Inhibition of diacylglycerol kinase to augment adoptive T cell transfer

Disclosed is a method of treating a solid tumor, where the tumor contains regions of hypoxic cells, either because of poor vascularization in the tumor or because of vasoconstrictive or vaso-occlusive measures brought to bear on the tumor. The method includes administering to a subject, a compound effective to activate protein kinase C activity in the cells of the tumor, via a route effective to direct the compound to such regions of hypoxia in the tumor. Preferred compounds include phorbol esters, diacylglycerols, and thapsigargin. Also disclosed is a vaso-occlusive composition containing a protein kinase C activator, for use in the treatment method.

The Board of Trustees of the Leland Stanford Junior University

Tumor treatment method

Novel iodinated and radioiodinated 1,2-diacylglycerol analogues are biological reagents for studying the effect of diacylglycerols in the activation of protein kinase C. This calcium-requiring enzyme may be involved in tumor promotion by phorbol diesters and related compounds. Iodinated and radioiodinated 1,2-diacylglycerol analogues, in accordance with the invention, are useful as imaging agents, such as radiopaques and radiopharmaceuticals, and have the general formula: ##STR1## The triglycerol backbone structure is 1,2-disubstituted with one position being occupied by an iodine-containing substituent, preferably an amino-substituted-2,4,6-triiodophenyl aliphatic chain, such as iopanoic acid, or by a monoiodiphenyl aliphatic chain, such as (m-iodophenyl)propanoic acid. The other position may be substituted with saturated and unsaturated long and short aliphatic chains.

The University of Michigan

Radioiodinated diacylglycerol analogues and methods of use

Disclosed are compounds of Formula (I): ##STR00001## or a salt thereof, wherein: R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and m are defined herein. Also disclosed are methods of using such compounds to inhibit the activity of one or both of diacylglycerol kinase alpha (DGK.alpha.) and diacylglycerol kinase zeta (DGK.zeta.), and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.

diacylglycerol/rak

Inhibition of diacylglycerol kinase to augment adoptive T cell transfer

Tumor treatment method

Radioiodinated diacylglycerol analogues and methods of use

Substituted naphthyridinone compounds useful as T cell activators

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