IP Library › Granted Patent US 12698512
Granted Patent B2
US 12698512 · App. 18/939,460 · Granted Aug 4, 2026

Methods comprising oncolytic viruses expressing CD19T and bispecific T cell engagers

Inventors: Saul J. Priceman (Valley Village, CA); Anthony K. Park (Pomona, CA); Yuman Fong (Pasadena, CA); Monil Shah (Sydney, AU)
Assignees: City of Hope; Imugene Limited
C12N15/86A61K39/001112A61K39/39541A61K39/39558A61P35/00C07K14/70503C07K16/2803C07K16/2809A61K2039/505A61K2039/5256C07K2317/31C12N2710/24143C12N2710/24171
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Quick Facts
Patent No.
US 12698512
App. No.
18/939,460
Granted
Aug 4, 2026
Kind
B2
Abstract

Described herein, inter alia, are oncolytic viruses expressing a truncated human CD19 (CD19t) and methods for treating a patient suffering from a solid tumor by administering an oncolytic virus expressing truncated human CD19 (OV19t), and optionally a T cell engager targeted to CD19.

Claims (39)

1 . A method of treating a subject having a solid tumor comprising:

administering to the subject an effective amount of an oncolytic virus expressing a truncated CD19 (OV19t), the nucleotide sequence of the OV19t comprising:

(a) a nucleotide sequence that is at least 99% identical to nucleotides 5,014-178,073 of SEQ ID NO: 1 over the entire length of nucleotides 5,014-178,073 of SEQ ID NO: 1; and

(b) encodes a truncated human CD19 (CD19t) comprising the amino acid sequence of SEQ ID NO:4; and

administering to the subject an effective amount of a bispecific T cell engager (TCE) that binds to CD19t and comprises:

(i) a CD19-targeted scFv comprising a variable heavy (VH) chain selected from SEQ ID NOs: 73, 81, and 89 and a variable light (VL) chain selected from SEQ ID NOs: 69, 77, and 85; and

(ii) a CD3-targeted scFv comprising a VH selected from SEQ ID NOs: 97, 113, 122, 103, and a VH comprising complementarity determining regions 1-3 (CDR1-CDR3) comprising SEQ ID NOs: 102-104, respectively, and a VL selected from SEQ ID NOs: 93, 109, 118, 126, and a VL comprising CDR1-CDR3 comprising SEQ ID NOs: 98-100, respectively.

2 . The method of claim 1 , wherein the nucleotide sequence of the OV19t is 99.5% identical to nucleotides 5,014-178,073 of SEQ ID NO: 1 over the entire length of nucleotides 5,014-178,073 of SEQ ID NO: 1.

3 . The method of claim 1 , wherein the nucleotide sequence of the OV19t is 99.9% identical to nucleotides 5,014-178,073 of SEQ ID NO: 1 over the entire length of nucleotides 5,014-178,073 of SEQ ID NO: 1.

4 . The method of claim 1 , wherein the nucleotide sequence of the OV19t is identical to nucleotides 5,014-178,073 of SEQ ID NO: 1 over the entire length of nucleotides 5,014-178,073 of SEQ ID NO: 1.

5 . The method of claim 1 , wherein the nucleotide sequence of the OV19t encodes SEQ ID NOs: 654, 670, 679, 680, 681, 685, 687, 689, 694, 705, 706, 708, 716, 718, 719, 729, 730, 732, 734, 735, 740, 743, 744, 745, 746, 757, 761, 763, 764, 769, 771, 773, 776, 781, 782, 783, 791, 793, 795, 796, 798, 799, 800, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 813, 814, 818, 821, 822, 823, 825, 826, 827, 828, 829, 830, 831, 834, 835, 839, 845, 846, 847, 848, 850, 851, 852, 856, 859, 864, 865, 869, 872, 873, 875, 876, 877, 878, 879, 880, 881, 882, 884, 885, 886, 887, 889, 891, 893, 894, 896, 897, 905, 906, 907, 910, 911, 912, 913, 914, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 927, and 928.

6 . The method of claim 1 , wherein the OV19t comprises a nucleotide sequence having no more than 100 single nucleotide changes compared to nucleotides 5,014-178,073 of SEQ ID NO: 1.

7 . The method of claim 1 , wherein the OV19t comprises a nucleotide sequence having no more than 50 single nucleotide changes compared to nucleotides 5,014-178,073 of SEQ ID NO: 1.

8 . The method of claim 1 , wherein the CD19t lacks a functional signaling domain.

9 . The method of claim 1 , wherein the TCE comprises an amino acid sequence selected from SEQ ID NOs: 931-934.

10 . The method of claim 1 , wherein the CD19-targeted scFv comprises a VH comprising SEQ ID NO: 73 and a VL comprising SEQ ID NO: 69.

11 . The method of claim 1 , wherein the CD19-targeted scFv comprises a VH comprising SEQ ID NO: 73 and a VL comprising SEQ ID NO: 77.

12 . The method of claim 1 , wherein the CD19-targeted scFv comprises a VH comprising SEQ ID NO: 89 and a VL comprising SEQ ID NO: 85.

13 . The method of claim 1 , wherein the CD3-targeted scFv comprises a VH comprising SEQ ID NO: 97 and a VL comprising SEQ ID NO: 93.

14 . The method of claim 1 , wherein the CD3-targeted scFv comprises:

a VH comprising a CDR1 comprising SEQ ID NO: 102, a CDR2 comprising SEQ ID NO: 103, and a CDR3 comprising SEQ ID NO: 104; and

a VL comprising a CDR1 comprising SEQ ID NO: 98, a CDR2 comprising SEQ ID NO: 99, and a CDR3 comprising SEQ ID NO: 100.

15 . The method of claim 1 , wherein the CD3-targeted scFv comprises a VH comprising SEQ ID NO: 113 and a VL comprising SEQ ID NO: 109.

16 . The method of claim 1 , wherein the solid tumor is colon cancer or rectal cancer.

17 . The method of claim 1 , wherein the CD19 scFv comprises a VH comprising SEQ ID NO: 73 and a VL comprising SEQ ID NO: 69; and wherein the CD3-targeted scFv comprises a VH comprising SEQ ID NO: 97 and a VL comprising SEQ ID NO: 93.

18 . The method of claim 2 , wherein the CD19 scFv comprises a VH comprising SEQ ID NO: 73 and a VL comprising SEQ ID NO: 69; and wherein the CD 3 -targeted scFv comprises a VH comprising SEQ ID NO: 97 and a VL comprising SEQ ID NO: 93.

19 . The method of claim 3 , wherein the CD19 scFv comprises a VH comprising SEQ ID NO: 73 and a VL comprising SEQ ID NO: 69; and wherein the CD3-targeted scFv comprises a VH comprising SEQ ID NO: 97 and a VL comprising SEQ ID NO: 93.

20 . The method of claim 4 , wherein the CD19 scFv comprises a VH comprising SEQ ID NO: 73 and a VL comprising SEQ ID NO: 69; and wherein the CD3-targeted scFv comprises a VH comprising SEQ ID NO: 97 and a VL comprising SEQ ID NO: 93.

21 . The method of claim 5 , wherein the CD19 scFv comprises a VH comprising SEQ ID NO: 73 and a VL comprising SEQ ID NO: 69; and wherein the CD3-targeted scFv comprises a VH comprising SEQ ID NO: 97 and a VL comprising SEQ ID NO: 93.

22 . The method of claim 6 , wherein the CD19 scFv comprises a VH comprising SEQ ID NO: 73 and a VL comprising SEQ ID NO: 69; and wherein the CD3-targeted scFv comprises a VH comprising SEQ ID NO: 97 and a VL comprising SEQ ID NO: 93.

23 . The method of claim 7 , wherein the CD19 scFv comprises a VH comprising SEQ ID NO: 73 and a VL comprising SEQ ID NO: 69; and wherein the CD3-targeted scFv comprises a VH comprising SEQ ID NO: 97 and a VL comprising SEQ ID NO: 93.

24 . The method of claim 16 , wherein the CD19 scFv comprises a VH comprising SEQ ID NO: 73 and a VL comprising SEQ ID NO: 69; and wherein the CD3-targeted scFv comprises a VH comprising SEQ ID NO: 97 and a VL comprising SEQ ID NO: 93.

25 . The method of claim 2 , wherein the TCE comprises an amino acid sequence selected from SEQ ID NOs: 931-934.

26 . The method of claim 3 , wherein the TCE comprises an amino acid sequence selected from SEQ ID NOs: 931-934.

27 . The method of claim 4 , wherein the TCE comprises an amino acid sequence selected from SEQ ID NOs: 931-934.

28 . The method of claim 5 , wherein the TCE comprises an amino acid sequence selected from SEQ ID NOs: 931-934.

29 . The method of claim 6 , wherein the TCE comprises an amino acid sequence selected from SEQ ID NOs: 931-934.

30 . The method of claim 7 , wherein the TCE comprises an amino acid sequence selected from SEQ ID NOs: 931-934.

31 . The method of claim 16 , wherein the TCE comprises an amino acid sequence selected from SEQ ID NOs: 931-934.