Epigenetic targets for enhancing cancer immunotherapy
AssigneeDuke University
InventorsCharles A. Gersbach, Sean McCutcheon
Life of this patent
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Abstract
Disclosed herein are compositions and methods for modulating T cells. For example, the compositions and methods may be used to increase memory T cells. The compositions and method may be used in combination with Adoptive T Cell Therapy (ACT) to enhance the ACT.
Claims55
A composition comprising a modulator of a gene selected from ZNF217, ETS1, RBSN, PRDM1, GATA3, RUNX3, FOXP1, GF11, AHR, ZNF626, FOXP3, ARNT, MYC, SON, TBX21, DUX4, YBX1, ZC3H8, ZNF367, ZNF335, KCMF1, TET2, ZBTB1, ZFX, RUNX1, FOXO1, MBD2, YY1, DNMT1, IRF1, CTCF, GTF2B, and HIC1.
A DNA targeting composition comprising:
- a Cas9 protein or a fusion protein, wherein the fusion protein comprises two heterologous polypeptide domains, wherein the first polypeptide domain comprises a zinc finger protein or a TALE or a Cas12 protein or a Cas13 protein or a Cas9 protein, and wherein the second polypeptide domain has an activity selected from transcription activation activity, transcription repression activity, nuclease activity, base editing activity, prime editing activity, transcription release factor activity, histone modification activity, nucleic acid association activity, methylase activity, and demethylase activity;
- and
- at least one guide RNA (gRNA) that targets the Cas9 protein to a target gene or a regulatory element thereof when the DNA targeting composition comprises a Cas9 protein, wherein the target gene is selected from ZNF217, ETS1, RBSN, PRDM1, GATA3, RUNX3, FOXP1, GF11, AHR, ZNF626, FOXP3, ARNT, MYC, SON, TBX21, DUX4, YBX1, ZC3H8, ZNF367, ZNF335, KCMF1, TET2, ZBTB1, ZFX, RUNX1, FOXO1, MBD2, YY1, DNMT1, IRF1, CTCF, GTF2B, and HIC1.
The composition of any one of claims 30-35, wherein the fusion protein comprises the amino acid sequence of SEQ ID NO:
- 43, or any fragment thereof,
- and/or wherein the fusion protein is encoded by a polynucleotide comprising the sequence of SEQ ID NO:
- 44,
- and/or wherein the fusion protein comprises an amino acid sequence having at least 90% or greater identity to SEQ ID NO:
- 43, or any fragment thereof,
- and/or wherein the fusion protein is encoded by a polynucleotide comprising a sequence having at least 90% or greater identity to SEQ ID NO:
- 44, or any fragment thereof,
- and/or wherein the fusion protein comprises an amino acid sequence having one, two, three, four, five or more changes selected from amino acid substitutions, insertions, or deletions, relative to SEQ ID NO:
- 43, or any fragment thereof,
- and/or wherein the fusion protein is encoded by a polynucleotide comprising a sequence having one, two, three, four, five or more changes selected from nucleotide substitutions, insertions, or deletions, relative to SEQ ID NO:
- 44.
A composition for increasing T cells, the composition comprising an inhibitor of a gene selected from ZNF217, ETS1, RBSN, PRDM1, GATA3, RUNX3, FOXP1, GF11, AHR, ZNF626, FOXP3, ARNT, MYC, SON, TBX21, DUX4, YBX1, ZC3H8, ZNF367, ZNF335, KCMF1, TET2, ZBTB1, ZFX, or RUNX1.
A composition for increasing T cells, the composition comprising an activator of a gene selected from FOXO1, MDB2, YY1, DNMT1, IRF1, CTCF, GTF2B, or HIC1.
Dependencies are inferred from the claim text.