Compositions and methods for treating cancer with DuoCARs
Inventors
Orentas, Rimas J. • Schneider, Dina • Haso, Waleed M. • Miltenyi, Stefan • Dropulic , Boro
Assignees
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Publication Number
US-11802142-B2
Publication Date
2023-10-31
Expiration Date
Abstract
Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.
Core Innovation
The patent describes an immunotherapy composition comprising at least one multi-cistronic vector, where a promoter is operably linked to a multi-cistronic nucleic acid sequence encoding two or more functional CARs. Each CAR includes an extracellular antigen binding domain, a transmembrane domain, and one or more non-identical intracellular signaling motifs, and the at least one multi-cistronic vector is used to genetically modify one or more lymphocyte populations.
The patent further describes a pharmaceutical composition containing an antitumor effective amount of a population of human lymphocytes, where each cell includes at least one multi-cistronic vector that encodes two or more functional CARs. In each multi-cistronic vector, the CAR components are covalently linked, including the extracellular antigen binding domain, the transmembrane domain, at least one linker domain, and one or more non-identical intracellular signaling motifs.
The described approach is framed as an antitumor immunotherapy using genetically modified human lymphocytes. The patent context includes DuoCAR-based multi-cistronic CAR architectures, including systems in which multiple antigen-binding capabilities are combined within CAR T cells via multi-cistronic vector encoding.
Claims Coverage
The provided independent claims center on multi-cistronic vectors encoding two or more functional CARs with non-identical intracellular signaling motifs and their use to genetically modify human lymphocyte populations, including an antitumor-effective human lymphocyte pharmaceutical composition. Across the claims, there are two inventive feature groupings.
Multi-cistronic car-encoding immunotherapy composition
An immunotherapy composition comprising at least one multi-cistronic vector comprising a promoter operably linked to a multi-cistronic nucleic acid sequence encoding two or more functional CARs, where each CAR comprises an extracellular antigen binding domain, a transmembrane domain, and one or more non-identical intracellular signaling motifs, and wherein the at least one multi-cistronic vector is used to genetically modify one or more lymphocyte populations.
Antitumor pharmaceutical composition of multi-cistronic car lymphocytes
A pharmaceutical composition comprising an antitumor effective amount of a population of human lymphocytes, wherein each cell of the population comprises at least one multi-cistronic vector; wherein each multi-cistronic vector encodes two or more functional CARs comprising a non-identical amino acid sequence independently selected from the group consisting of SEQ ID NOs. 54, 56, 60, and 62; and wherein each CAR comprises an extracellular antigen binding domain, a transmembrane domain, at least one linker domain, and one or more non-identical intracellular signaling motifs, with the components covalently linked in each CAR.
Across both independent claims, the claimed inventive scope is multi-cistronic vector encoding of two or more functional CARs in genetically modified lymphocytes, where the CARs include non-identical intracellular signaling motifs selected from specified SEQ ID NOs and the CAR domains are covalently linked in each multi-cistronic vector. The second independent claim additionally specifies an antitumor-effective amount for a population of human lymphocytes.
Stated Advantages
Improved in vivo expansion, persistence, and/or relapse prevention.
Documented Applications
Leukemia applications including use with CAR antigen targets such as CD19, CD20, and CD22, and antitumor-effective pharmaceutical compositions for leukemia/lymphoma indications including chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML).
Lymphoma applications including mantle cell lymphoma, non-Hodgkin's lymphoma, and Hodgkin's lymphoma.
Multiple myeloma applications using T cells from a human with multiple myeloma.
Adult carcinoma applications using T cells from adults with selected adult carcinomas, including oral/pharynx, digestive system, respiratory system, bones/joints, soft tissue, skin, central nervous system, breast, genital, urinary, eye/orbit, endocrine, and brain cancers.
Non-tumor applications including inflammatory/autoimmune and infectious diseases.
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