Abstract: Herein are provided anti-CD22 single domain antibodies (sdAb) prepared by immunizing a llama with the extracellular domain of the predominant human CD22 isoform. By constructing a library of the heavy chain repertoire generated, VHH antibodies specific to the immunogen were isolated. The 27 example antibodies initially produced comprise CDR1, CDR2, and CDR3 sequences corresponding, respectively to SEQNOs: 1-3, 4-6, 7-9, 10-12, 13-15, 16-18, 19-21, 22-24, 25-27, 28-30, 31-33, 34-36, 37-39, 40-42, 43-45, 46-48, 49-51, 52-54, 55-57, 58-60, 61-63, 64-66, 67-69, 70-72, 73-75, 75-78, and 79-81; and related sequences. Also provided are multivalent antibodies comprising any one of the sdAbs, including bispecific T-cell engagers, bispecific killer cell engagers (BiKEs), and trispecific killer cell engagers (TrikEs). Also described are chimeric antigen receptors (CARs) for CAR-T therapy comprising any one of the aforementioned sdAbs. Uses of these molecules in the treatment of cancer are also described.

Abstract: The present disclosure relates to antigen-binding agents that specifically bind to epidermal growth factor receptor variant III (EGFRvIII). Antigen-binding agents of the present disclosure include antibodies and antigen-binding fragments thereof, chimeric antigen receptors (CARs) and bi-specific T-cell engagers (BiTE!), bispecific killer cell engagers (BiKEs) and trispecific killer cell engagers (TrikEs). Nucleic acid molecules and vectors expressing antibodies, antigen-binding fragments. CARs, BiTEs, BiKEs or TriKEs are also encompassed by the present disclosure. Immune cells engineered to express CARs, BiTEs, BiKEs or TriKEs may be used to specifically recognize and kill cells expressing EGFRvIII.

Abstract: Here is disclosed isolated or purified monoclonal antibodies, or an antigen-binding fragments thereof, which binds to human CD3, and which comprises: a CDRH1 amino acid sequence of SEQ ID NO: 150, a CDRH2 amino acid sequence of SEQ ID NO: 151, a CDRH3 amino acid sequence of SEQ ID NO: 152, a CDRL1 amino acid sequence of SEQ ID NO: 153, a CDRL2 amino acid sequence of SEQ ID NO: 154, and a CDRL3 amino acid sequence of SEQ ID NO: 155. Also provided are recombinant polypeptides comprising said monoclonal antibody, or an antigen-binding fragment thereof, such as multivalent antibodies, including bispecific T-cell engagers. Also described are chimeric antigen receptors (CARs) for CAR-T therapy comprising any one of the monoclonal antibodies, or antigen-binding fragments thereof. Nucleic acids encoding the aforementioned antibodies, fragments, and polypeptides are also disclosed, along with therapeutic applications in the treatment of and autoinflammatory disease or cancer.

Abstract: Herein are provided anti-BCMA single domain antibodies (sdAb) prepared byte immunizing a llama with the ecto-domain of human B-cell maturation antigen (BCMA) that is preferentially expressed by mature B lymphocytes. By constructing a library of the heavy chain repertoire generated, VHH antibodies specific to the immunogen were isolated. The 13 unique example antibodies initially produced comprise CDR1, CDR2, and CDR3 sequences corresponding, respectively to SEQ NOs: 1-3, 4-6, 7-9, 10-12, 13-15, 16-18, 19-21, 22-24, 25-27, 28-30, 31-33, 34-36, 37-39; and related sequences. Also provided are multivalent antibodies comprising any one of the sdAbs, including bispecific T-cell engagers, bispecific killer cell engagers (BiKEs), and trispecific killer cell engagers (TriKEs). Also described are chimeric antigen receptors (CARs) for CAR-T therapy comprising any one of the aforementioned sdAbs.

Abstract: Herein are provided anti-EGFR single domain antibodies (sdAb) prepared by immunizing a llama with recombinant human EGFRvIII. VHH antibodies specific to EGFR were isolated. The example antibodies initially produced comprise CDR1, CDR2, and CDR3 sequences corresponding, respectively to SEQ NOs: 1-3, 4-6, 7-9, 10-12, 13-15, 16-18, 19-21, 22-24, 25-27, 28-30, 31-33, 34-36, 37-39, 40-42, 43-45, and 46-48; and related sequences, including humanized variants. Also provided are multivalent antibodies comprising any one of the sdAbs, including bispecific T-cell engagers, bispecific killer cell engagers (BiKEs), and trispecific killer cell engagers (TriKEs). Also described are chimeric antigen receptors (CARs) for CAR-T therapy comprising any one of the aforementioned sdAbs. Uses of these molecules in the treatment of cancer are also described, in particularly EGFR-high cancers. Hinge lengths may be selected to achieve desired activities, such as high activity or high selectivity for target vs. non-target cells.

Abstract: The present disclosure relates to a single domain antibody that specifically binds to the epitope in the catalytic domain of carbonic anhydrase IX (CA-IX). The single domain antibody has a dissociation constant (KD) of 1×10?7 or lower for a monomeric form of human CA-IX and/or a dimeric form of human CA-IX.

Abstract: Herein are provided anti-CD22 single domain antibodies (sdAb) prepared by immunizing a llama with the extracellular domain of the predominant human CD22 isoform. By constructing a library of the heavy chain repertoire generated, VHH antibodies specific to the immunogen were isolated. The 27 example antibodies initially produced comprise CDR1, CDR2, and CDR3 sequences corresponding, respectively to SEQNOs: 1-3, 4-6, 7-9, 10-12, 13-15, 16- 18, 19-21, 22-24, 25-27, 28-30, 31-33, 34-36, 37-39, 40-42, 43-45, 46-48, 49-51, 52-54, 55- 57, 58-60, 61-63, 64-66, 67-69, 70-72, 73-75, 75-78, and 79-81; and related sequences. Also provided are multivalent antibodies comprising any one of the sdAbs, including bispecific T-cell engagers, bispecific killer cell engagers (BiKEs), and trispecific killer cell engagers (TriKEs). Also described are chimeric antigen receptors (CARs) for CAR-T therapy comprising any one of the aforementioned sdAbs. Uses of these molecules in the treatment of cancer are also described.

Abstract: The present disclosure relates to antigen-binding agents that specifically bind to epidermal growth factor receptor variant III (EGFRvIII). Antigen-binding agents of the present disclosure include antibodies and antigen-binding fragments thereof, chimeric antigen receptors (CARs) and bi-specific T-cell engagers (BITE!), bispecific killer cell engagers (BiKEs) and bispecific killer cell engagers (TriKEs). Nucleic acid molecules and vectors expressing antibodies, antigen-binding fragments, CARs, BiTEs, BiKEs or TriKEs are also encompassed by the present disclosure. Immune cells engineered to express CARs, BiTEs, BiKEs or TriKEs may be used to specifically recognize and kill cells expressing EGFRvIII.