T cells expressing membrane-anchored il-12 for the treatment of cancer
AssigneeBoard of Regents, The University of Texas System
InventorsShulin LI, Jiemiao HU, Xueqing XIA
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Abstract
Provided herein are polypeptides comprising membrane-anchored IL-12. Also provided herein are T cells expressing the membrane-anchored IL-12. Further, methods of treating cancer comprising administering T cells expressing membrane-anchored IL-12 are provided herein. Also provided are combination treatments comprising T cells expressing membrane-anchored IL-12 and T cell chemoattractant-inducing chemokines. In addition, methods are provided for activating T cells to express NKG2D and methods of their use in the treatment of cancer.
Claims102
A membrane-anchored interleukin 12 (IL-12) heterodimer protein comprising:
- a) a first polypeptide comprising an IL-12 alpha subunit p35 or a polypeptide at least 90% similar thereto;
- b) a second polypeptide comprising an IL-12 beta subunit p40 or a polypeptide at least 90% similar thereto;
- and
- c) a transmembrane domain fused to a terminus of the first polypeptide and/or the second polypeptide.
A method of treating a cancer in a subject comprising administering an effective amount of T cells engineered to express membrane-anchored IL-12 to the subject.
An in vitro method for generating NKG2D-positive CD8+ T cells comprising:
- (a) obtaining a starting population of T cells;
- and
- (b) culturing the starting population of T cells in the presence of anti-CD3 and CD80 for a period of time sufficient to induce NKG2D expression, thereby generating NKG2D+CD8+ T cells.
Dependencies are inferred from the claim text.