Antigen binding constructs to CD3
Antigen binding constructs that bind to CD3, for example antibodies, including antibody fragments (such as minibodies and cys-diabodies) that bind to CD3, are described herein. Methods of use are described herein.
1. A nucleic acid comprising a nucleotide sequence encoding a polypeptide comprising:
a variable light (VL) domain comprising an amino acid sequence of SEQ ID NO:3;
a variable heavy (VH) domain comprising an amino acid sequence of SEQ ID NO: 6 or 86;
a linker comprising an amino acid sequence of SEQ ID NO: 98, wherein the linker links the VL and the VH domains;
a C H 3; and
a hinge region linking the VH domain to the C H 3.
2. A nucleic acid comprising a nucleotide sequence encoding a humanized antigen binding construct, wherein the humanized antigen binding construct comprises:
a HCDR1 of the HCDR1 in SEQ ID NO: 6 or 86;
a HCDR2 of the HCDR2 in SEQ ID NO: 6 or 86;
a HCDR3 of the HCDR3 in SEQ ID NO: 6 or 86;
a LCDR1 of the LCDR1 in SEQ ID NO: 3;
a LCDR2 of the LCDR2 in SEQ ID NO: 3; and
a LCDR3 of the LCDR3 in SEQ ID NO: 3,
wherein the humanized antigen binding construct binds specifically to CD3,
wherein the humanized antigen binding construct comprises a humanized minibody or a humanized cys-diabody, and
wherein the human antigen binding construct further comprises at least one of:
a LFR3 of the LFR3 in SEQ ID NO: 3; or
a HFR3 of the HFR3 in SEQ ID NO: 6 or 86.
3. The nucleic acid of claim 2 , wherein the antigen binding construct comprises the humanized minibody.
4. The nucleic acid of claim 2 , wherein the antigen binding construct comprises a heavy chain variable domain that is a heavy chain variable domain in SEQ ID NO: 86, and a light chain variable domain that is a light chain variable domain in SEQ ID NO: 3.
5. The nucleic acid of claim 4 , wherein the nucleic acid comprises a sequence at least about 80% identical to SEQ ID NO: 85.
6. The nucleic acid of claim 2 , wherein the antigen binding construct comprises a heavy chain variable domain that is a heavy chain variable domain in SEQ ID NO: 6, and a light chain variable domain that is a light chain variable domain in SEQ ID NO: 3.
7. The nucleic acid of claim 6 , wherein the nucleic acid comprises a sequence at least about 80% identical to SEQ ID NO: 83.
8. A vector comprising a nucleic acid of claim 2 .
9. A nucleic acid comprising a nucleotide sequence encoding a humanized OKT3 minibody that binds to CD3, the humanized minibody comprising a polypeptide that comprises:
a single-chain variable fragment (scFv) that binds to CD3, the scFv comprising a variable heavy (VH) domain linked to a variable light (VL) domain,
wherein the scFv comprises a LFR3 of the LFR3 in SEQ ID NO: 3, or a HFR3 of the HFR3 in SEQ ID NO: 6 or 86, or both;
a hinge;
a human IgG C H 3 sequence;
a HCDR1 of the HCDR1 in SEQ ID NO: 6 or 86;
a HCDR2 of the HCDR2 in SEQ ID NO: 6 or 86;
a HCDR3 of the HCDR3 in SEQ ID NO: 6 or 86;
a LCDR1 of the LCDR1 in SEQ ID NO: 3;
a LCDR2 of the LCDR2 in SEQ ID NO: 3; and
a LCDR3 of the LCDR3 in SEQ ID NO: 3.
10. A nucleic acid comprising a nucleotide sequence encoding a humanized minibody that binds to CD3, wherein the humanized minibody comprises:
a polypeptide that comprises:
a single-chain variable fragment (scFv) that binds to CD3, the scFv comprising a variable heavy (VH) domain linked to a variable light (VL) domain,
wherein the scFv comprises a LFR3 of the LFR3 in SEQ ID NO: 3, or a HFR3 of the HFR3 in SEQ ID NO: 6 or 86, or both;
a hinge;
a human IgG C H 3 sequence;
a HCDR1 of the HCDR1 in SEQ ID NO: 6 or 86;
a HCDR2 of the HCDR2 in SEQ ID NO: 6 or 86;
a HCDR3 of the HCDR3 in SEQ ID NO: 6 or 86;
a LCDR1 of the LCDR1 in SEQ ID NO: 3;
a LCDR2 of the LCDR2 in SEQ ID NO: 3; and
a LCDR3 of the LCDR3 in SEQ ID NO: 3.