| CPC A61K 40/4215 (2025.01) [A61K 40/11 (2025.01); A61K 40/15 (2025.01); A61K 40/31 (2025.01); A61K 48/005 (2013.01); A61P 35/00 (2018.01); C07K 14/7051 (2013.01); C07K 16/2809 (2013.01); C07K 16/2878 (2013.01); C12N 15/86 (2013.01); A61K 2239/13 (2023.05); C07K 2317/622 (2013.01); C12N 2740/15022 (2013.01); C12N 2740/15023 (2013.01); C12N 2740/15043 (2013.01); C12N 2830/48 (2013.01); C12N 2830/50 (2013.01)] | 25 Claims |
|
1. A recombinant lentiviral particle comprising:
(a) a viral envelope comprising (i) a vesicular stomatitis Indiana virus envelope glycoprotein (VSIV-G) comprising amino acid substitutions selected from the group consisting of: K47A and R354A; K47A and R354Q; K47Q and R354A; and K47Q and R354Q; and (ii) a non-viral membrane-bound tropism polypeptide comprising an anti-CD3ε scFv and a human CD8α hinge and transmembrane domain; and
(b) a recombinant lentiviral vector comprising a polynucleotide encoding a myeloproliferative sarcoma virus enhancer, negative control region deleted, d1587rev primer-binding site substituted (MND) U3 promoter or an EF1α promoter operably linked to a polynucleotide encoding a signal peptide and an anti-BCMA chimeric antigen receptor comprising an anti-BCMA scFv comprising a heavy chain variable region (VH) comprising a CDRH1, a CDRH2, and a CDRH3 comprising the amino acid sequences of SEQ ID NOs: 82, 83, and 84, and a light chain variable region (VL) comprising a CDRL1, a CDRL2, and a CDRL3 comprising the amino acid sequences of SEQ ID NOs: 86, 87, and 88; a CD8α hinge and transmembrane domain; a CD137 costimulatory domain; and a CD3ζ primary signaling domain.
|