T cell manufacturing compostions and methods
AssigneesBiontech US Inc., Stichting Het Nederlands Kanker Instituut—Antoni Van Leeuwenhoek Ziekenhis
InventorsMarit M. VAN BUUREN, Divya Reddy LENKALA, Joost Huibert VAN DEN BURG, Jessica Kohler, Matthew GOLDSTEIN, Ed Fritsch, Renate DE BOER, Ton SCHUMACHER, Noor BAKKER
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Abstract
The generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.
Claims23
-54. (canceled)
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 one or more cancer antigen epitope sequences expressed by 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 the 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 human biological sample, or
- (ii) at least 0.1% of the 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 human biological sample.
Dependencies are inferred from the claim text.