T cell compositions with improved phenotypic properties

Abstract

The present invention provides an isolated cell composition, which in some embodiments is suitable for adoptive immunotherapy, as well as methods of manufacturing the cell compositions and methods of treatment with the cell compositions. The composition comprises, in a pharmaceutically acceptable carrier, at least about 10 6 CD8+ T cells specific for target peptide antigen(s), which comprises T memory stem (T SCM ) cells. In various embodiments, the composition is from about 1% to about 100% T memory stem cells, providing for a robust and durable adoptive therapy, as well as providing for T cell engineering advances.

1 . An isolated cell composition suitable for adoptive immunotherapy, the composition comprising, in a pharmaceutically acceptable carrier: at least 10 6  CD8+ T cells specific for one or more target peptide antigens, and comprising T memory stem (T SCM ) cells. 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The isolated cell composition of  claim 1 , wherein the target peptide antigens are tumor associated antigens, tumor derived neoantigens, or tumor specific neoantigens. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The isolated cell composition of  claim 1 , comprising CD8+ T cells specific for at least five target peptide antigens. 
     
     
         8 . (canceled) 
     
     
         9 . The isolated cell composition of  claim 1 , wherein the cell composition is at least 90% T cells. 
     
     
         10 . (canceled) 
     
     
         11 . The isolated cell composition of  claim 1 , wherein at least 10% of the CD8+ T cells are specific for a target peptide antigen. 
     
     
         12 - 14 . (canceled) 
     
     
         15 . The isolated cell composition of  claim 4 , wherein the cell composition further comprises CD8+ T cells specific for bacterial, viral, and/or fungal pathogens. 
     
     
         16 . The isolated cell composition of  claim 15 , wherein the CD8+ T cells specific for bacterial, viral, or fungal pathogens include T cells specific for antigens of influenza, CMV, EBV, and/or adenovirus. 
     
     
         17 . (canceled) 
     
     
         18 . The isolated cell composition of  claim 1 , wherein the CD8+ T cells are from about 1% to about 50% T memory stem cells. 
     
     
         19 . (canceled) 
     
     
         20 . The isolated cell composition of  claim 18 , wherein the CD8+ T cells are at least 5% T memory stem cells. 
     
     
         21 - 22 . (canceled) 
     
     
         23 . The isolated cell composition of  claim 1 , wherein the T cells specific for the one or more target antigens are at least 15% T memory stem cells. 
     
     
         24 . The isolated cell composition of  claim 1 , wherein greater than 95% of the CD8+ T cells comprise a memory phenotype. 
     
     
         25 . (canceled) 
     
     
         26 . The isolated cell composition of  claim 24 , wherein the CD8+ T cells are at least 30% central and effector memory T cells. 
     
     
         27 . The isolated cell composition of  claim 24 , wherein the CD8+ T cells are at least 50% central and effector memory T cells, or wherein the CD8+ T cells specific for the one or more target antigens are at least 50% central and effector memory T cells. 
     
     
         28 - 30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . The isolated cell composition of  claim 1 , wherein the CD8+ T cells are less than 20% terminally differentiated, and wherein the composition comprises less than 30% naive T cells (T N ). 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . The isolated cell composition of  claim 33 , wherein the composition comprises less than 15% naive cells. 
     
     
         37 - 38 . (canceled) 
     
     
         39 . The isolated cell composition of  claim 1 , wherein at least 10% of the CD8+ T cells display a polyfunctional phenotype upon activation. 
     
     
         40 - 41 . (canceled) 
     
     
         42 . The isolated cell composition of  claim 1 , wherein the cell composition is less than 10% CD4+ T cells. 
     
     
         43 - 46 . (canceled) 
     
     
         47 . The isolated cell composition of  claim 1 , wherein the composition further comprises γδ T cells. 
     
     
         48 - 52 . (canceled) 
     
     
         53 . The isolated cell composition of  claim 47 , wherein the γδ T cells comprise Vδ1 and Vδ2 cells. 
     
     
         54 . (canceled) 
     
     
         55 . The isolated cell composition of  claim 1 , wherein the composition is produced by enrichment of CD8+ T cells specific for the target peptide antigens from source cells; and/or expansion of CD8+ T cells specific for the target peptide antigens from source cells. 
     
     
         56 - 62 . (canceled) 
     
     
         63 . The isolated cell composition of  claim 55 , wherein the antigen-specific T cells are enriched by aAPCs having an MHC class I ligand and optionally a co-stimulatory ligand. 
     
     
         64 - 65 . (canceled) 
     
     
         66 . The isolated cell composition of  claim 63 , wherein the enrichment is magnetic enrichment with paramagnetic aAPCs, and wherein the cells and aAPCs are optionally incubated in the presence of a magnetic field for at least one minute, and wherein the enriched cells are expanded in culture for from 1 to 4 weeks. 
     
     
         67 - 68 . (canceled) 
     
     
         69 . (canceled) 
     
     
         70 . The isolated cell composition of  claim 66 , wherein the cells are expanded in culture in the presence of one or more cytokines or growth factors selected from MIP-1β, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-10, IL-15, IL-21, and INF-γ. 
     
     
         71 - 79 . (canceled) 
     
     
         80 . The isolated cell composition of  claim 70 , wherein the cells are expanded in culture in the presence of IL-2, IL-4, IL-6, INF-γ, and IL-1β. 
     
     
         81 . The isolated cell composition of  claim 1 , wherein one or more target peptide antigens are selected from peptide epitopes of Survivin, WT-1, PRAME, and Cyclin A1. 
     
     
         82 . The isolated cell composition of  claim 1 , wherein one or more target peptide antigens are selected from peptide epitopes of PR3, XBP1-US, XBP1-SP, CD138, CS1, NY-ESO1, SOX2, EBV, Influenza, CMV, RHAMM, Mart-1/Melan A, gp100, CMVpp65, and Influenza Matrix Protein M1. 
     
     
         83 . An isolated cell composition suitable for adoptive immunotherapy, the composition comprising, in a pharmaceutically acceptable carrier:
 at least 70% CD8+ T cells and less than 5% CD4+ T cells;   at least 5% of the CD8+ cells are T memory stem (T SCM ) cells;   at least 30% of the CD8+ cells are central and effector memory T cells;   less than 10% of the CD8+ T cells are terminally differentiated T cells; and   less than 10% of the CD8+ cells are naive cells.   
     
     
         84 - 97 . (canceled) 
     
     
         98 . A method for treating a patient with cancer, comprising administering the cell composition of  claim 1  to a patient in need. 
     
     
         99 - 104 . (canceled) 
     
     
         105 . (canceled) 
     
     
         106 - 113 . (canceled) 
     
     
         114 . A method for making a population of γδ T cells, comprising, expanding a population of T cells in the presence of two or more of IL-2, IL-4, IL-6, INF-γ, and IL-1β. 
     
     
         115 - 127 . (canceled)