Compositions for treating cancer
Inventors
Friedman, Kevin M. • Perkins, Molly R. • Dobson, Connor S. • SAZINSKY, Stephen L. • Contrastano, Shannon G. • Thompson Beura, Emily • Ahonen, Cory • Avery, Andrew
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12440564-B2
Publication Date
2025-10-14
Expiration Date
Abstract
The present disclosure provides compositions and methods comprising recombinant particles suitable for specifically delivering one or more chimeric antigen receptors to immune effector cells in vivo.
Core Innovation
The invention relates to a recombinant lentiviral particle for delivering an anti-BCMA chimeric antigen receptor. The particle includes a viral envelope and a recombinant lentiviral vector in which a promoter is operably linked to a polynucleotide encoding a signal peptide and the anti-BCMA CAR, with the anti-BCMA CAR comprising an anti-BCMA scFv having specified heavy chain variable region and light chain variable region components, a CD8α hinge and transmembrane domain, a CD137 costimulatory domain, and a CD3 primary signaling domain.
For the viral envelope, the invention specifies a vesicular stomatitis Indiana virus envelope glycoprotein with particular amino acid substitutions or a mutated viral envelope glycoprotein defined by specific SEQ ID NOs. In addition, the viral envelope includes a non-viral membrane-bound tropism polypeptide comprising an anti-CD38 scFv fused to a human CD8α hinge and transmembrane domain or specified by SEQ ID NOs.
The lentiviral vector is defined by specific lentiviral regulatory elements, including LTR regions, Ψ packaging signal, cPPT/FLAP, and rev response element, and optionally a woodchuck hepatitis virus posttranscriptional regulatory element. The promoter is an MND U3 promoter or an EF1α promoter, and the recombinant lentiviral vector further includes 3′ LTR comprising U3 and R regions, a polyadenylation signal, and a poly(A) tail.
Claims Coverage
The independent claims recite three main inventive feature groupings: a specified viral envelope with mutated envelope glycoprotein and a non-viral membrane-bound tropism polypeptide; a recombinant lentiviral vector with specified lentiviral regulatory elements and promoter(s); and expression of an anti-BCMA chimeric antigen receptor with defined CDR sequences and specified signaling architecture. Across the independent claims, the coverage centers on recombinant lentiviral particles defined by these envelope and vector features.
Specified VSIV-G substitutions with anti-CD38 membrane tropism polypeptide
A viral envelope comprising a vesicular stomatitis Indiana virus envelope glycoprotein with amino acid substitutions selected from K47A and R354A; K47A and R354Q; K47Q and R354A; and K47Q and R354Q, and a non-viral membrane-bound tropism polypeptide comprising an anti-CD38 scFv and a human CD8α hinge and transmembrane domain.
MND U3 or EF1α promoter driving anti-BCMA CAR with CD137 and CD3
A recombinant lentiviral vector comprising an MND U3 promoter or an EF1α promoter operably linked to a polynucleotide encoding a signal peptide and an anti-BCMA chimeric antigen receptor comprising specified VH and VL CDR amino acid sequences, a CD8α hinge and transmembrane domain, a CD137 costimulatory domain, and a CD3 primary signaling domain.
Defined lentiviral regulatory elements with anti-BCMA CAR sequence
A recombinant lentiviral vector comprising 5′ and 3′ LTR regions, Ψ packaging signal, cPPT/FLAP, RRE, and optionally WPRE, with an MND promoter or EF1α promoter operably linked to a polynucleotide encoding a signal peptide and an anti-BCMA CAR comprising a specified amino acid sequence.
Mutated envelope glycoprotein and non-viral tropism polypeptide specified by SEQ ID NOs
A viral envelope comprising a mutated viral envelope glycoprotein and a non-viral membrane-bound tropism polypeptide comprising amino acid sequences set forth in specified SEQ ID NOs, together with the lentiviral vector features described above.
Across the independent claims, the core coverage is a recombinant lentiviral particle defined by a viral envelope combining a specified VSIV-G or mutated viral envelope glycoprotein with a non-viral membrane-bound tropism polypeptide containing an anti-CD38 scFv, together with a recombinant lentiviral vector containing defined lentiviral regulatory elements and a promoter driving expression of an anti-BCMA CAR with CD8α hinge/transmembrane, CD137 costimulatory domain, and CD3 primary signaling domain.
Stated Advantages
Provides in vivo cancer treatment by delivering anti-BCMA chimeric antigen receptors to immune effector cells using recombinant lentiviral particles.
Documented Applications
In vivo cancer treatment using recombinant lentiviral particles delivering anti-BCMA chimeric antigen receptors to immune effector cells.
Treatment context includes multiple myeloma, including relapsed/refractory.
Interested in licensing this patent?