Immunotherapy for direct reprogramming of cancer cells into immune cells/antigen presenting cells/dendritic cells

Patent metadata

Field	Value
Publication number	US-2023046425-A1
Application number	US-202017788519-A
Country	US
Kind code	A1
Filing date	Dec 22, 2020
Priority date	Dec 23, 2019
Publication date	Feb 16, 2023
Grant date	—

Abstract

Described are compounds and compositions for transdifferentiation of glioblastoma cells to antigen presenting cells. Methods of using the compounds and compositions to treat glioblastoma and to induce an immune response against a glioblastoma are also described.

First claim

1 . A method of treating glioblastoma comprising: administering to the glioblastoma in a subject one or more nucleic acids that increase and/or decrease expression of one or more glioblastoma to antigen presenting cell transdifferentiation determinants thereby increasing and/or decreasing expression of one or more of the transdifferentiation determinants in glioblastoma cells of the glioblastoma.

2 . The method of claim 1 , wherein the glioblastoma is a high-grade glioma or a glioblastoma multiforme.

3 . The method of claim 1 or 2 , wherein increasing and/or decreasing expression of the one or more transdifferentiation determinants in the glioblastoma cells results in transdifferentiation of one or more of the glioblastoma cells into antigen presenting cells.

4 . The method of claim 1 or 2 , wherein increasing and/or decreasing expression of the one or more transdifferentiation determinants in the glioblastoma cells results in reduced growth rate of the glioblastoma cells.

5 . The method of any one of claim 1 - 4 , wherein the one or more transdifferentiation determinants are selected from the list consisting of: SPI1, IKZF1, CTSZ, AEBP1, ARID3A, ATF5, ATP8B2, BASP1, BCL11B, BCL6, BID, CBFA2T3, CIITA, CIR1, CREG1, CTTN, EGR1, ELF4, ETS1, ETV5, FOXP1, FOXP4, GATA3, GM2A, GNS, GTF2IRD1, HHEX, HOXB3, HTATIP2, IRF5, IRF8, KIF21A, KLF4, KLF11, KLF12, KMT2E, LDB1, LEF1, LMO2, LOXL2, MAGED1, MMP14, MREG, MXD1, MYBL1, NAB2, NCOA3, NFATC2, NFE2L1, NOTCH2, NR1H3, PAWR, PCGF2, PDLIM1, PLAGL1, PLCG1, POU6F1, PRKCB, PTPN14, RB1, RBFOX2, RBPMS, RORA, RUNX3, SALL2, SATB1, SOX13, STAT6, TCF7, TCF19, TDP2, TFEB, TFEC, TLE2, TSHZ2, USF1, USF2, ZBTB34, ZEB1, ZFP91, ZNF74, ZNF280B, ZNF366, ZNF483, ZNF507, ZNF827, AES, ARF2, ATOX1, BATF3, BCL11A, CBFA2T3, CEBPA, CEBPB, PPARD, ETV3, ETV6, GLMP, HELZ2, ID2, IKZF3, MAFB, MAZ, MYCL, POU2AF1, SPIB, TAF10, TFE3, VAV1, and ZFP384.

6 . The method of claim 5 , wherein the one or more transdifferentiation determinants are selected from the list consisting of: IRF5, CBFA2T3, IRF8, ATOX1, SPI1, BCL11A, ID2, MYCL, BATF3, HHEX, SPIB, VAV1, ETV6, MXD1, ETV3, LMO2, AES, GLMP, CEBPA, MAZ, TFE3, CEBPB, POU2AF1, HELZ2, IKZF3, MAFB, ARF2, PPARD, TAF10, and ZFP384.

7 . The method of claim 5 , wherein the glioblastoma is a human glioblastoma and the one or more transdifferentiation determinants are selected from the list consisting of: SPI1, IKZF1, CTSZ, AEBP1, ARID3A, ATF5, ATP8B2, BASP1, BCL11B, BCL6, BID, CBFA2T3, CIITA, CIR1, CREG1, CTTN, EGR1, ELF4, ETS1, ETV5, FOXP1, FOXP4, GATA3, GM2A, GNS, GTF2IRD1, HHEX, HOXB3, HTATIP2, IRF5, IRF8, KIF21A, KLF4, KLF11, KLF12, KMT2E, LDB1, LEF1, LMO2, LOXL2, MAGED1, MMP14, MREG, MXD1, MYBL1, NAB2, NCOA3, NFATC2, NFE2L1, NOTCH2, NR1H3, PAWR, PCGF2, PDLIM1, PLAGL1, PLCG1, POU6F1, PRKCB, PTPN14, RB1, RBFOX2, RBPMS, RORA, RUNX3, SALL2, SATB1, SOX13, STAT6, TCF7, TCF19, TDP2, TFEB, TFEC, TLE2, TSHZ2, USF1, USF2, ZBTB34, ZEB1, ZFP91, ZNF74, ZNF280B, ZNF366, ZNF483, ZNF507, ZNF827.

8 . The method of any one of claims 1 - 7 , wherein the method comprises administering to the glioblastoma one or more nucleic acids that increase and/or decrease expression of one or more glioblastoma to antigen presenting cell transdifferentiation determinants thereby increasing and/or decreasing expression of one or more of the transdifferentiation determinants in glioblastoma cells of the glioblastoma.

9 . The method of claim 8 , wherein two or more transdifferentiation determinants are selected from the group consisting of: SPI1, IKZF1, IRF8, ATOX1, BCL11A, ID2, BATF3, IKZF3 and GATA3.

10 . The method of claim 9 wherein the two or more transdifferentiation determinants comprise SPI1 and IKZF1.

11 . The method of claim 10 , wherein the method further comprises administering a nucleic acid encoding one or more of ID2, IRF8, BATF3, ATOX1, and BCL11A.

12 . A method for transdifferentiation of glioblastoma cells into antigen presenting cells comprising: administering to the glioblastoma cells one or more nucleic acids that increase and/or decrease expression of one or more glioblastoma to antigen presenting cell transdifferentiation determinants thereby increasing and/or decreasing expression of one or more of the transdifferentiation determinants in the glioblastoma cells.

13 . The method of claim 12 , wherein the glioblastoma cell is a high-grade glioma cell or a glioblastoma multiforme cell.

14 . The method of claim 12 or 13 , wherein the antigen presenting cells are dendritic cell-like or macrophage-like.

15 . The method of any one of claims 12 - 14 , wherein the one or more transdifferentiation determinants are selected from the list consisting of: SPI1, IKZF1, CTSZ, AEBP1, ARID3A, ATF5, ATP8B2, BASP1, BCL11B, BCL6, BID, CBFA2T3, CIITA, CIR1, CREG1, CTTN, EGR1, ELF4, ETS1, ETV5, FOXP1, FOXP4, GATA3, GM2A, GNS, GTF2IRD1, HHEX, HOXB3, HTATIP2, IRF5, IRF8, KIF21A, KLF4, KLF11, KLF12, KMT2E, LDB1, LEF1, LMO2, LOXL2, MAGED1, MMP14, MREG, MXD1, MYBL1, NAB2, NCOA3, NFATC2, NFE2L1, NOTCH2, NR1H3, PAWR, PCGF2, PDLIM1, PLAGL1, PLCG1, POU6F1, PRKCB, PTPN14, RB1, RBFOX2, RBPMS, RORA, RUNX3, SALL2, SATB1, SOX13, STAT6, TCF7, TCF19, TDP2, TFEB, TFEC, TLE2, TSHZ2, USF1, USF2, ZBTB34, ZEB1, ZFP91, ZNF74, ZNF280B, ZNF366, ZNF483, ZNF507, ZNF827, AES, ARF2, ATOX1, BATF3, BCL11A, CBFA2T3, CEBPA, CEBPB, PPARD, ETV3, ETV6, GLMP, HELZ2, ID2, IKZF3, MAFB, MAZ, MYCL, POU2AF1, SPIB, TAF10, TFE3, VAV1, and ZFP384.

16 . The method of claim 15 , wherein the one or more transdifferentiation determinants are selected from the list consisting of: IRF5, CBFA2T3, IRF8, ATOX1, SPI1, BCL11A, ID2, MYCL, BATF3, HHEX, SPIB, VAV1, ETV6, MXD1, ETV3, LMO2, AES, GLMP, CEBPA, MAZ, TFE3, CEBPB, POU2AF1, HELZ2, IKZF3, MAFB, ARF2, PPARD, TAF10, and ZFP384.

17 . The method of claim 15 , wherein the glioblastoma is a human glioblastoma and the one or more transdifferentiation determinants are selected from the list consisting of: SPI1, IKZF1, CTSZ, AEBP1, ARID3A, ATF5, ATP8B2, BASP1, BCL11B, BCL6, BID, CBFA2T3, CIITA, CIR1, CREG1, CTTN, EGR1, ELF4, ETS1, ETV5, FOXP1, FOXP4, GATA3, GM2A, GNS, GTF2IRD1, HHEX, HOXB3, HTATIP2, IRF5, IRF8, KIF21A, KLF4, KLF11, KLF12, KMT2E, LDB1, LEF1, LMO2, LOXL2, MAGED1, MMP14, MREG, MXD1, MYBL1, NAB2, NCOA3, NFATC2, NFE2L1, NOTCH2, NR1H3, PAWR, PCGF2, PDLIM1, PLAGL1, PLCG1, POU6F1, PRKCB, PTPN14, RB1, RBFOX2, RBPMS, RORA, RUNX3, SALL2, SATB1, SOX13, STAT6, TCF7, TCF19, TDP2, TFEB, TFEC, TLE2, TSHZ2, USF1, USF2, ZBTB34, ZEB1, ZFP91, ZNF74, ZNF280B, ZNF366, ZNF483, ZNF507, ZNF827.

18 . The method of any one of claims 12 - 17 , wherein the method comprises administering to the glioblastoma two or more nucleic acids that increase and/or decrease expression of two or more transdifferentiation determinants.

19 . The method of claim 18 , wherein the two or more transdifferentiation determinants are selected from the group consisting of: SPI1, IKZF1, IRF8, ATOX1, BCL11A, ID2, BATF3, IKZF3, and GATA3.

20 . The method of claim 19 , wherein the two or more transdifferentiation determinants comprise SPI1 and IKZF1.

21 . The method of claim 20 , wherein the method further comprises administering a nucleic acid encoding one or more of ID2, IRF8, BATF3, ATOX1, and BCL11A.

22 . The method of any one of claims 1 - 21 , wherein the one or more nucleic acids is provided in a non-viral vector, plasmid, DNA vector, RNA vector, viral vector, or a lentiviral vector.

23 . The method of any one of claims 1 - 11 , wherein the glioblastoma is in the brain or spina

Assignees

• Univ Florida

Inventors

• Tran David
• Le Son

Classifications

• C12N5/0693 Primary

  Tumour cells; Cancer cells · CPC title

• C12N2510/00

  Genetically modified cells · CPC title

• C12N15/63

  Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C12N2501/22

  Colony stimulating factors (G-CSF, GM-CSF) · CPC title