US 12,258,581 B2
T cell manufacturing compositions and methods
Marit M. Van Buuren, Belmont, MA (US); Divya Reddy Lenkala, Watertown, MA (US); Joost Huibert Van Den Burg, Amsterdam (NL); Jessica Kohler, Boston, MA (US); Matthew Goldstein, Jamaica Plain, MA (US); Ed Fritsch, Concord, MA (US); Renate De Boer, Diemen (NL); Ton Schumacher, Aloemehomal (NL); and Noor Bakker, Stuyvesantstraat (NL)
Assigned to BioNTech US Inc., Cambridge, MA (US); and Stichting Het Nederlands Kanker Instituut—Antoni Van Leeuwenhoek Ziekenhis, Amsterdam (NL)
Filed by BioNTech US Inc., Cambridge, MA (US); and STICHTING HET NEDERLANDS KANKER INSTITUUT—ANTONI VAN LEEUWENHOEK ZIEKENHIS, Amsterdam (NL)
Filed on Oct. 5, 2021, as Appl. No. 17/494,633.
Application 17/494,633 is a continuation of application No. 16/735,555, filed on Jan. 6, 2020, granted, now 11,162,072.
Application 16/735,555 is a continuation of application No. PCT/US2018/059896, filed on Nov. 8, 2018.
Claims priority of provisional application 62/737,625, filed on Sep. 27, 2018.
Claims priority of provisional application 62/618,445, filed on Jan. 17, 2018.
Claims priority of provisional application 62/588,590, filed on Nov. 20, 2017.
Claims priority of provisional application 62/583,229, filed on Nov. 8, 2017.
Prior Publication US 2022/0177840 A1, Jun. 9, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 5/0783 (2010.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01)
CPC C12N 5/0636 (2013.01) [A61K 39/4611 (2023.05); A61K 39/464401 (2023.05); A61K 39/46449 (2023.05); A61P 35/00 (2018.01); A61K 2039/572 (2013.01); C12N 2501/26 (2013.01); C12N 2501/998 (2013.01)] 21 Claims
 
1. A method of preparing cancer antigen-specific T cells ex vivo suitable for T cell therapy in a human subject, the method comprising:
(a) depleting CD25+ cells from a population of immune cells comprising antigen presenting cells (APCs) and T cells, thereby forming a depleted population of immune cells comprising a first population of APCs and T cells, wherein the population of immune cells is from a biological sample from a human subject; and
(b) incubating the depleted population of immune cells for a first time period in the presence of:
(i) FMS-like tyrosine kinase 3 receptor ligand (FLT3L), and
(ii) (A) a polypeptide comprising one or more cancer antigen epitope sequences expressed by cancer cells of a human subject with cancer; or (B) a polynucleotide encoding the polypeptide comprising the one or more cancer antigen epitope sequences expressed by the cancer cells of the human subject with cancer; thereby forming a population of stimulated T cells; and
(c) expanding the population of stimulated T cells, thereby forming an expanded population of T cells, wherein expanding comprises expanding T cells derived from naïve CD8+ T cells or naïve CD4+ T cells; wherein the expanded population of T cells comprises T cells that are specific to a complex comprising (i) a first cancer antigen epitope sequence of the one or more cancer antigen epitope sequences and (ii) an MHC protein expressed by the cancer cells or APCs of the human subject with cancer; wherein:
(i) at least 0.1% of CD8+ T cells that are specific to the complex in the expanded population of T cells are derived from the naïve CD8+ T cells from the biological sample from the human subject, or
(ii) at least 0.1% of CD4+ T cells that are specific to the complex in the expanded population of T cells are derived from the naïve CD4+ T cells from the biological sample from the human subject.