Single-domain antibodies against CD33 and constructs thereof

Inventors

ZHANG, Yafeng • ZHAN, Tailan • Sun, Fei • Liu, Jian • Zhang, Qing • Wu, Shu

Assignees

Legend Biotech USA Inc

Abstract

The present application provides single-domain antibodies targeting CD33 and constructs thereof, including chimeric receptors, immune effector cell engagers and immunoconjugates. Further provided are engineered immune cells (such as T cells) comprising an anti-CD33 chimeric receptor and optionally a second chimeric receptor targeting a second antigen or epitope. Pharmaceutical compositions, kits and methods of treating cancer are also provided.

Core Innovation

The invention relates to an anti-CD33 construct comprising a single domain antibody (sdAb) moiety that specifically binds to CD33. The sdAb moiety is defined by CDR1 comprising the amino acid sequence of SEQ ID NO: 18, CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and CDR3 comprising the amino acid sequence of SEQ ID NO: 22. The disclosure further encompasses anti-CD33 sdAb CDR compositions with sequence-definition features, including variants defined by substitution limits and/or % identity thresholds.

The disclosed concepts extend to engineered receptor and multi-target binding formats for cancer immunotherapy. These include constructs in which the anti-CD33 sdAb forms part of chimeric receptors with extracellular sdAb domains, a transmembrane domain, and an intracellular signaling domain, including CD3z and additional co-stimulatory motifs such as 4-1BB and CD28. The disclosure also covers dual, tandem, multispecific, and split CAR systems, and second antigen/epitope target formats.

The invention further encompasses engineered immune cells expressing these anti-CD33-based receptors, together with nucleic acids and vectors encoding the constructs. The disclosure also includes pharmaceutical compositions containing the constructs, immunoconjugate concepts involving an anti-CD33 sdAb and an effector molecule, and methods of treating cancer through administration of an effective amount. The disclosed cancer context includes acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndromes (MDS).

Claims Coverage

The independent claim defines an anti-CD33 sdAb construct with specific CDR sequence definitions for CDR1, CDR2, and CDR3, yielding coverage of a core anti-CD33 binding moiety. Dependent claims refine this independent claim by adding sequence identity constraints, specifying multi-domain CAR-like architectures, and expanding to second binding moieties, immunoconjugate formats, and cancer treatment by administration.

Overall claim coverage centers on an anti-CD33 sdAb construct defined by specific CDR1, CDR2, and CDR3 sequences, with additional coverage for sequence identity-limited sdAb variants, defined extracellular/transmembrane/intracellular signaling architectures, second binding moieties targeting CLL1 or CD123, immunoconjugate formats with an effector molecule, and administering the construct to treat cancer.

Stated Advantages

Documented Applications