Epigenetic Signature of T Cell Aging and Malignancy
AssigneesSt. Jude Children's Research Hospital, Regents of the University of Minnesota
InventorsBenjamin A. Youngblood, Caitlin C. Zebley, Tian Mi, David Masopust, Andrew G. Soerens
Life of this patent
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Abstract
A 139-gene epigenetic signature for use in. methods for assessing the age and longevity of a T cell, selecting a T cell for a T cell therapy, and/or determining a T-cell acute lymphoblastic leukemia subtype is provided.
Claims15
A method for assessing the age and longevity of a T cell comprising determining an average methylation of a plurality of genes in the T cell, the plurality of genes selected from the group consisting of:
- Ebf3, Irx5, Pou3f3, Irs2, Irx3, Ctbp2, Efna5, Tle1, Sall1, Foxd3, Zfp423, Hmga2, Sox1, Afdn, Nr2f2, Nkx6-1, Zfp316, Kctd15, Sox11, Sox4, Spry2, Cbln1, Tshz3, Zfp503, Tfap2c, Inhbb, Irx2, Gas1, Fat4, Nkx2-4, Zcchc14, Cadm1, Pcdh10, Onecut2, Prdm6, Mycn, Fzd8, Epha7, Sox9, Nkx2-1, Epb4114b, Dio3, Otx1, Zbtb10, Jag1, Nkx6-2, Tbx3, Tbx18, Agap1, Foxc2, Sox2, Foxe1, Fzd1, Insm2, Adra2c, Gm13375, Nfib, Foxg1, Ptpn3, Mtcl1, Ube2ql1, Zfp536, AI606473, Pitx2, Zfp521, Grb10, Lin28b, Gpr27, Cacna2d3, Zic4, Fam78b, Begain, Gm9748, Gm5468, Prox1, Schip1, Bhlhe22, Cdh2, Fat1, Twist1, Ptprg, Sdk2, Bmp4, Mn1, Gm30731, Nova1, Grid1, Zfhx3, Gli3, Magi1, Pax3, Ccdc85c, Bnc2, Mkx, Id4, Auts2, Tlx3, Shisa6, Ctnnd2, Trank1, Fam19a5, Chsy3, Lrp12, Hoxd8, Lrig1, Tenm4, Flt1, Kcnn2, Pcdh17, Reln, Pou3f1, Lrrc4, Chst15, Large1, Fezf1, Gab1, Plcb4, Cdh4, Cilp2, Prickle1, Sox3, Smco4, Fgfr2, Hoxd11, Skor2, Fignl2, Cnr1, Nbea, Trim71, Snap91, Sox14, Kcnk9, Mpped2, Sema6a, Pde5a, Wnt5a, Grip1, Dmrt3, and Adgrl3,
- wherein an average hypermethylation of the plurality of genes in the T cell as compared to a control naïve T cell is indicative of the age and longevity of the T cell.
A method for selecting a T cell for a T cell therapy comprising determining an average methylation of a plurality of genes in the T cell, the plurality of genes selected from the group consisting of:
- Ebf3, Irx5, Pou3f3, Irs2, Irx3, Ctbp2, Efna5, Tle1, Sall1, Foxd3, Zfp423, Hmga2, Sox1, Afdn, Nr2f2, Nkx6-1, Zfp316, Kctd15, Sox11, Sox4, Spry2, Cbln1, Tshz3, Zfp503, Tfap2c, Inhbb, Irx2, Gas1, Fat4, Nkx2-4, Zcchc14, Cadm1, Pcdh10, Onecut2, Prdm6, Mycn, Fzd8, Epha7, Sox9, Nkx2-1, Epb41l4b, Dio3, Otx1, Zbtb10, Jag1, Nkx6-2, Tbx3, Tbx18, Agap1, Foxc2, Sox2, Foxe1, Fzd1, Insm2, Adra2c, Gm13375, Nfib, Foxg1, Ptpn3, Mtcl1, Ube2ql1, Zfp536, AI606473, Pitx2, Zfp521, Grb10, Lin28b, Gpr27, Cacna2d3, Zic4, Fam78b, Begain, Gm9748, Gm5468, Prox1, Schip1, Bhlhe22, Cdh2, Fat1, Twist1, Ptprg, Sdk2, Bmp4, Mn1, Gm30731, Nova1, Grid1, Zfhx3, Gli3, Magi1, Pax3, Ccdc85c, Bnc2, Mkx, Id4, Auts2, Tlx3, Shisa6, Ctnnd2, Trank1, Fam19a5, Chsy3, Lrp12, Hoxd8, Lrig1, Tenm4, Flt1, Kcnn2, Pcdh17, Reln, Pou3f1, Lrrc4, Chst15, Large1, Fezf1, Gab1, Plcb4, Cdh4, Cilp2, Prickle1, Sox3, Smco4, Fgfr2, Hoxd11, Skor2, Fignl2, Cnr1, Nbea, Trim71, Snap91, Sox14, Kcnk9, Mpped2, Sema6a, Pde5a, Wnt5a, Grip1, Dmrt3, and Adgrl3,
- wherein an average hypermethylation of the plurality of genes in the T cell as compared to a control naïve T cell is indicative of the use of the T cell in a T cell therapy.
A method for determining a T-cell acute lymphoblastic leukemia (T-ALL) subtype comprising determining an average methylation of a plurality of genes of the T-ALL cells, the plurality of genes selected from the group consisting of:
- Ebf3, Irx5, Pou3f3, Irs2, Irx3, Ctbp2, Efna5, Tle1, Sall1, Foxd3, Zfp423, Hmga2, Sox1, Afdn, Nr2f2, Nkx6-1, Zfp316, Kctd15, Sox11, Sox4, Spry2, Cbln1, Tshz3, Zfp503, Tfap2c, Inhbb, Irx2, Gas1, Fat4, Nkx2-4, Zcchc14, Cadm1, Pcdh10, Onecut2, Prdm6, Mycn, Fzd8, Epha7, Sox9, Nkx2-1, Epb41l4b, Dio3, Otx1, Zbtb10, Jag1, Nkx6-2, Tbx3, Tbx18, Agap1, Foxc2, Sox2, Foxe1, Fzd1, Insm2, Adra2c, Gm13375, Nfib, Foxg1, Ptpn3, Mtcl1, Ube2ql1, Zfp536, AI606473, Pitx2, Zfp521, Grb10, Lin28b, Gpr27, Cacna2d3, Zic4, Fam78b, Begain, Gm9748, Gm5468, Prox1, Schip1, Bhlhe22, Cdh2, Fat1, Twist1, Ptprg, Sdk2, Bmp4, Mn1, Gm30731, Nova1, Grid1, Zfhx3, Gli3, Magi1, Pax3, Ccdc85c, Bnc2, Mkx, Id4, Auts2, Tlx3, Shisa6, Ctnnd2, Trank1, Fam19a5, Chsy3, Lrp12, Hoxd8, Lrig1, Tenm4, Flt1, Kcnn2, Pcdh17, Reln, Pou3f1, Lrrc4, Chst15, Large1, Fezf1, Gab1, Plcb4, Cdh4, Cilp2, Prickle1, Sox3, Smco4, Fgfr2, Hoxd11, Skor2, Fignl2, Cnr1, Nbea, Trim71, Snap91, Sox14, Kcnk9, Mpped2, Sema6a, Pde5a, Wnt5a, Grip1, Dmrt3, and Adgrl3,
- wherein the average methylation of the plurality of genes in the T cell as compared to a control naïve T cell is indicative of the T-ALL subtype.
Dependencies are inferred from the claim text.