CD8-specific antibody constructs and compositions thereof
Inventors
Cruite, Patricia Ann • AMATYA, Shirisha • HARDING, Hugh • MacKenzie, Lauren Pepper
Assignees
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Publication Number
US-11535869-B2
Publication Date
2022-12-27
Expiration Date
Abstract
Disclosed herein are antibodies or antigen binding fragments thereof that specifically bind human CD8. Also disclosed are fusion proteins comprising a Henipavirus glycoprotein G and CD8 antibodies for targeting and transducing cells expressing CD8. Viral vectors and other compositions containing the fusion proteins, as well as methods of using the fusion proteins, are also disclosed.
Core Innovation
The invention relates to a viral vector targeting CD8+ T cells by combining an antibody fragment that binds CD8 with henipavirus envelope glycoprotein G (G protein) and a henipavirus F protein molecule or biologically active portion thereof. The vector further includes one or more nucleic acid sequences encoding a chimeric antigen receptor (CAR), linking CD8 targeting via the antibody fragment to a CAR cargo within a single targeting viral vector format.
The antibody fragment comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), defined by specified sets of SEQ ID NOs. The antibody fragment is attached to the C-terminus of the G protein or the biologically active portion thereof.
The patent also describes compositions and systems that include a lipid particle comprising an antibody fragment that binds CD8, together with a henipavirus G protein and a henipavirus F protein, plus a CAR. The content further identifies a method of treating cancer by administering an effective amount of such a lipid particle composition.
Claims Coverage
Two independent claims are identified: one directed to a viral vector targeting CD8+ T cells and one directed to a method of treating cancer using a lipid particle composition. Across the independent claims, the coverage centers on CD8-binding antibody fragments with defined HCDR/LCDR SEQ ID sets, henipavirus G and F components, and a CAR element.
C-terminus-attached CD8 antibody fragment with defined CDR SEQ ID sets
The antibody fragment binds CD8 and comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, HCDR3) and three light chain complementarity determining regions (LCDR1, LCDR2, LCDR3), wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise specified SEQ ID NO sets, and the antibody fragment is attached to the C-terminus of the G protein or biologically active portion thereof.
Henipavirus G protein combined with henipavirus F protein in a targeting vector
A viral vector includes a henipavirus envelope glycoprotein G (G protein) or a biologically active portion thereof and a henipavirus F protein molecule or biologically active portion thereof as components in the CD8-targeting construct.
CAR-encoding nucleic acid sequences included in the CD8-targeting viral vector
One or more nucleic acid sequences encoding a chimeric antigen receptor (CAR) are included in the viral vector.
Lipid particle composition for cancer treatment including CD8 antibody, henipavirus G and F, and CAR
A method of treating cancer administers to a subject an effective amount of a composition comprising a lipid particle comprising an antibody fragment that binds CD8, a henipavirus envelope glycoprotein G (G protein) or a biologically active portion thereof, a henipavirus F protein molecule or biologically active portion thereof, and a chimeric antigen receptor (CAR), wherein the antibody fragment contains defined HCDR1/HCDR2/HCDR3 and LCDR1/LCDR2/LCDR3 SEQ ID sets.
Across the independent claims, the inventive coverage is centered on CD8-binding antibody fragments with explicitly defined HCDR/LCDR SEQ ID sets, incorporation of henipavirus envelope glycoprotein G and henipavirus F as part of a single targeting construct, and inclusion of CAR elements. The therapeutic independent claim further specifies administration of a lipid particle composition containing these components.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating cancer by administering an effective amount of a lipid particle composition comprising an antibody fragment that binds CD8, a henipavirus envelope glycoprotein G, a henipavirus F protein, and a CAR.
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