US 12,133,866 B2
Anti third party central memory t cells, methods of producing same and use of same in transplantation and disease treatment
Yair Reisner, Houston, TX (US); Yaki Eidelstein, Rehovot (IL); Eran Ophir, Rehovot (IL); Assaf Lask, Rehovot (IL); Ran Afik, Rehovot (IL); Noga Or-Geva, Rehovot (IL); and Esther Bachar-Lustig, Rehovot (IL)
Assigned to Yeda Research and Development Co. Ltd., Rehovot (IL)
Filed by Yeda Research and Development Co. Ltd., Rehovot (IL)
Filed on May 3, 2022, as Appl. No. 17/735,146.
Application 15/825,275 is a division of application No. 14/343,053, abandoned, previously published as PCT/IL2012/050354, filed on Sep. 6, 2012.
Application 17/735,146 is a continuation of application No. 15/825,275, filed on Nov. 29, 2017, granted, now 11,324,777.
Claims priority of provisional application 61/532,172, filed on Sep. 8, 2011.
Prior Publication US 2023/0024587 A1, Jan. 26, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 35/17 (2015.01); A61K 35/12 (2015.01); A61K 35/22 (2015.01); A61K 35/26 (2015.01); A61K 35/28 (2015.01); A61K 35/34 (2015.01); A61K 35/36 (2015.01); A61K 35/38 (2015.01); A61K 35/39 (2015.01); A61K 35/407 (2015.01); A61K 35/42 (2015.01); A61K 39/00 (2006.01); C12N 5/0783 (2010.01)
CPC A61K 35/17 (2013.01) [A61K 35/22 (2013.01); A61K 35/26 (2013.01); A61K 35/28 (2013.01); A61K 35/34 (2013.01); A61K 35/36 (2013.01); A61K 35/38 (2013.01); A61K 35/39 (2013.01); A61K 35/407 (2013.01); A61K 35/42 (2013.01); A61K 39/001 (2013.01); C12N 5/0636 (2013.01); C12N 5/0637 (2013.01); A61K 2035/122 (2013.01); A61K 2035/124 (2013.01); A61K 2039/5158 (2013.01); C12N 2501/2307 (2013.01); C12N 2501/2315 (2013.01); C12N 2501/2321 (2013.01); C12N 2502/1121 (2013.01)] 19 Claims
 
1. A method of treating an autoimmune disease in a subject in need thereof, the method comprising:
(i) generating an isolated population of cells comprising non-graft versus host (GVH) inducing anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, said cells being tolerance-inducing cells and capable of homing to the lymph nodes following administration to the subject, by a method comprising:
(a) treating peripheral blood mononuclear cells (PBMC) derived from a donor with an agent capable of depleting CD4+ and CD56+ cells so as to obtain CD8+ T cells;
(b) contacting said CD8+ T cells with a third-party antigen or antigens in the presence of IL-21 so as to allow enrichment of antigen reactive cells;
(c) adding IL-15 and IL-7 to said culture comprising said antigen reactive cells, said third party antigen or antigens and said IL-21 of step (b); and
(d) culturing said cells resulting from step (c) in the presence of IL-21, IL-15 and IL-7 in an antigen free environment so as to allow proliferation of cells comprising said Tcm phenotype;
(ii) transplanting into the subject immature hematopoietic cells derived from said donor; and
(iii) administering to the subject a therapeutically effective amount of said isolated population of cells,
thereby treating the subject.