Oncolytic virus expressing a car T cell target and uses thereof
Inventors
Fong, Yuman • Priceman, Saul J. • Forman, Stephen J. • Chen, Nanhai • Park, Anthony K.
Assignees
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Publication Number
US-12364724-B2
Publication Date
2025-07-22
Expiration Date
Abstract
An oncolytic poxvirus encoding a truncated human CD19 is used in conjunction with a chimeric antigen receptor to treat solid tumors.
Core Innovation
The disclosed invention provides a recombinant oncolytic virus engineered to express a truncated human CD19 that lacks a functional signaling domain. The truncated CD19 comprises the amino acid sequence identified as SEQ ID NO:29 and is encoded by a nucleotide sequence operably linked to a promoter for expression in infected cells.
The recombinant oncolytic virus includes insertion of the truncated CD19 nucleotide sequence into the J2R locus of an oncolytic virus. The oncolytic virus has nucleotide sequence at least 99% identical to SEQ ID NO:1 and lacks a sequence encoding thymidine kinase.
By combining the virus with CD19-directed CAR T cells, the document describes a strategy in which infected solid tumor cells display the truncated CD19 to enable killing by CD19 CAR T cells. The recombinant virus is described in the context of CAR-targeted human CD19 T cells, including schedules for administration and specified cancer indications including solid tumors, ovarian cancer, and pancreatic cancer.
Claims Coverage
The provided content includes one independent claim centered on a recombinant oncolytic virus encoding a truncated CD19 lacking a functional signaling domain and inserted into the J2R locus under promoter control, using an oncolytic virus at least 99% identical to SEQ ID NO:1 but lacking thymidine kinase. Additional dependent claims specify the promoter type and recite combination treatment with CAR targeted CD19 T cells for solid tumor indications.
Recombinant oncolytic virus expressing truncated human CD19 in J2R locus
A recombinant oncolytic virus comprising a nucleotide sequence encoding a truncated human CD19 lacking a functional signaling domain and comprising the amino acid sequence SEQ ID NO:29, wherein the nucleotide sequence encoding the truncated CD19 is operably linked to a promoter and is inserted into the J2R locus of an oncolytic virus comprising nucleotide sequence at least 99% identical to SEQ ID NO:1 and lacking a sequence encoding thymidine kinase.
Viral early promoter-controlled CD19t expression
The recombinant oncolytic virus wherein the promoter is a viral early promoter.
Poxvirus early promoter-controlled CD19t expression
The recombinant oncolytic virus wherein the promoter is a poxvirus early promoter.
Combination with CD19 CAR T cells
A method of treating cancer comprising administering the recombinant oncolytic virus and administering a T cell population expressing a CAR targeted to human CD19, simultaneously or subsequently.
Timing of T cell administration
The T cell population is administered 1-20 days after administration of the recombinant oncolytic virus.
Solid tumor, ovarian cancer, or pancreatic cancer indication
The solid tumor is ovarian cancer or pancreatic cancer.
Overall, the claims coverage focuses on a recombinant oncolytic virus carrying a promoter-controlled truncated CD19 expression cassette inserted into the J2R locus of a thymidine-kinase-lacking, highly SEQ ID NO:1-identical oncolytic virus. The dependent claims narrow promoter class to viral early and poxvirus early promoters and cover combination treatment with CAR targeted CD19 T cells, including a specified T-cell timing window and solid tumor indications of ovarian cancer and pancreatic cancer.
Stated Advantages
Documented Applications
Treating cancer by administering the recombinant oncolytic virus and a T cell population expressing a CAR targeted to human CD19.
Use in solid tumor treatment, including ovarian cancer and pancreatic cancer.
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