US 12,031,156 B2
T cell receptor-deficient T cell compositions
Charles L. Sentman, Grantham, NH (US)
Assigned to TRUSTEES OF DARTMOUTH COLLEGE, Hanover, NH (US)
Filed by TRUSTEES OF DARTMOUTH COLLEGE, Hanover, NH (US)
Filed on May 12, 2020, as Appl. No. 16/872,419.
Application 16/872,419 is a division of application No. 15/948,303, filed on Apr. 9, 2018, granted, now 10,689,618.
Application 15/948,303 is a division of application No. 14/676,028, filed on Apr. 1, 2015, granted, now 9,938,497, issued on Apr. 10, 2018.
Application 14/676,028 is a division of application No. 13/502,978, granted, now 9,181,527, issued on Nov. 10, 2015, previously published as PCT/US2010/054846, filed on Oct. 29, 2010.
Claims priority of provisional application 61/255,980, filed on Oct. 29, 2009.
Prior Publication US 2020/0339950 A1, Oct. 29, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 5/0783 (2010.01); A61K 35/17 (2015.01); A61K 39/00 (2006.01); A61K 35/12 (2015.01)
CPC C12N 5/0636 (2013.01) [A61K 35/17 (2013.01); A61K 39/0011 (2013.01); A61K 2035/124 (2013.01); A61K 2039/5156 (2013.01); A61K 2039/585 (2013.01); C12N 2501/515 (2013.01); C12N 2510/02 (2013.01); C12N 2511/00 (2013.01)] 19 Claims
 
1. A method of producing one or more compositions comprising human T cells which express a heterologous ligand binding domain or a heterologous receptor other than a T cell receptor (TCR), wherein said human T cells are derived from primary human T cells and wherein said method comprises: (i) obtaining one or more compositions comprising isolated primary human T cells, each of said compositions being comprised of primary human T cells isolated from at least one human donor; (ii) modifying the primary human T cells comprised in said one or more compositions comprising primary human T cells in order to functionally impair or reduce expression of one or more components of the TCR complex endogenously expressed by said human primary T cells; and (iii) modifying the primary human T cells in the one or more compositions comprising human T cells by introducing a nucleic acid which encodes a desired exogenous ligand binding domain or a desired exogenous receptor, wherein said exogenous ligand binding domain and exogenous receptor do not comprise a TCR and further wherein said exogenous ligand binding domain or exogenous receptor directly or indirectly mediates T cell signaling upon binding of the ligand binding domain or the exogenous receptor to a ligand expressed by a target cell; thereby producing one or more compositions comprising human T cells which express at least one desired ligand binding domain or desired receptor and further wherein one or more components of the TCR complex endogenously expressed by said human primary T cells is functionally impaired or the expression of one or more components of the TCR complex endogenously expressed by said human primary T cells is reduced.