T cell manufacturing compositions and methods
AssigneesBiontech US Inc., Stichting Het Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis
InventorsMarit M. van Buuren, Divya Reddy Lenkala, Jessica Kohler, Flavian Duvalle Brown, Christina Murphy Kuksin, Joost Huibert van den Berg, Renate de Boer, Noor Bakker, Ton Schumacher, John Haanen
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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.
Claims18
A method of treating a cancer in a human subject in need thereof, comprising:
- (a) depleting CD14+ cells and/or CD25+ cells from a washed and/or cryopreserved peripheral blood mononuclear cell (PBMC) sample from the human subject comprising antigen presenting cells (APCs) and T cells, thereby forming a CD14 and/or CD25 depleted PBMCs comprising a first population of APCs and T cells;
- (b) incubating the first population of APCs and T cells from step (a) for a first time period in the presence of:
- (i) FMS-like tyrosine kinase 3 receptor ligand (FLT3L), and
- (ii) (A) a polypeptide comprising at least two different tumor antigen epitope sequences expressed by cancer cells of a human subject with cancer, or (B) a polynucleotide encoding the polypeptide comprising the at least two different tumor antigen epitope sequences expressed by cancer cells of the human subject with cancer, and wherein the at least two different tumor antigen epitope sequences are not expressed in non-cancer cells of the human subject;
- thereby forming a population of cells comprising stimulated T cells;
- (c) expanding the stimulated T cells from step (b), thereby forming an expanded population of cells comprising tumor antigen-specific T cells,
- wherein the tumor antigen-specific T cells comprise T cells that are specific to a complex comprising (i) a tumor antigen epitope sequence of the at least two different tumor antigen epitope sequences from step (b)(ii), and (ii) an MHC protein expressed by the cancer cells or APCs of the human subject;
- and
- (d) administering the expanded population of cells from (c) to the human subject, wherein the human subject:
- (i) has unresectable melanoma,
- (ii) has previously received a PD-1 inhibitor or PD-L1 inhibitor and a CTLA-4 inhibitor containing regimen and has disease progression, or
- (iii) has received or is currently receiving a PD-1 inhibitor or PD-L1 inhibitor for at least 3 months and has stable disease or asymptomatic progressive disease.
Dependencies are inferred from the claim text.