ANTIGEN BINDING CONSTRUCTS TO CD8
Antigen binding constructs that bind to CD8, for example antibodies, including antibody fragments (such as scFv, minibodies, and cys-diabodies) that bind to CD8, are described herein. Methods of use are described herein.
1 . An antigen binding construct that comprises:
a HCDR1 of a HCDR1 of SEQ ID NO: 3 or 6;
a HCDR2 of HCDR1 of SEQ ID NO: 3 or 6;
a HCDR3 of HCDR1 of SEQ ID NO: 3 or 6;
a LCDR1 of LCDR1 of SEQ ID NO: 9;
a LCDR2 of LCDR1 of SEQ ID NO: 9; and
a LCDR3 of LCDR1 of SEQ ID NO: 9.
2 . The antigen binding construct of claim 1 , wherein the antigen binding construct binds specifically to CD8.
3 . The antigen binding construct of claim 1 , further comprising a detectable marker.
4 . The antigen binding construct of claim 1 , further comprising a therapeutic agent.
5 . The antigen binding construct of claim 1 , wherein the antigen binding construct is bispecific.
6 . The antigen binding construct of claim 1 , wherein the antigen binding construct is a monovalent scFv.
7 . A humanized cys-diabody that binds to CD8, the humanized cys-diabody comprising a polypeptide that comprises:
a single-chain variable fragment (scFv) comprising a variable heavy (V H ) domain linked to a variable light (V L ) domain; and
a C-terminal cysteine.
8 . The humanized cys-diabody of claim 7 , wherein the order of the variable domains, from N terminus to C terminus of the polypeptide is V L , V H .
9 . The humanized cys-diabody of claim 7 , wherein the order of the variable domains, from N terminus to C terminus of the polypeptide is V H , V L .
10 . The humanized cys-diabody of claim 7 , further comprising a detectable molecule.
11 . The humanized cys-diabody of claim 7 , wherein the humanized cys-diabody comprises:
a HCDR1 of a HCDR1 of SEQ ID NO: 3 or 6;
a HCDR2 of HCDR1 of SEQ ID NO: 3 or 6;
a HCDR3 of HCDR1 of SEQ ID NO: 3 or 6;
a LCDR1 of LCDR1 of SEQ ID NO: 9;
a LCDR2 of LCDR1 of SEQ ID NO: 9; and
a LCDR3 of LCDR1 of SEQ ID NO: 9.
12 . A humanized minibody that binds to CD8, the humanized minibody comprising a polypeptide that comprises from N-terminus to C-terminus:
a single-chain variable fragment (scFv) that binds to CD8, the scFv comprising a variable heavy (V H ) domain linked to a variable light (V L ) domain;
a hinge-extension domain comprising a human IgG1 hinge region; and
a human IgG C H 3 sequence.
13 . The humanized minibody of claim 12 , further comprising a detectable marker.
14 . The humanized minibody of claim 12 , wherein the humanized minibody comprises:
a HCDR1 of a HCDR1 of SEQ ID NO: 3 or 6;
a HCDR2 of HCDR1 of SEQ ID NO: 3 or 6;
a HCDR3 of HCDR1 of SEQ ID NO: 3 or 6;
a LCDR1 of LCDR1 of SEQ ID NO: 9;
a LCDR2 of LCDR1 of SEQ ID NO: 9; and
a LCDR3 of LCDR1 of SEQ ID NO: 9.
15 . A nucleic acid encoding an antibody of claim 1 .
16 . A cell line producing an antibody of claim 1 .
17 . A kit comprising:
an antigen binding construct of claim 1 ; and
a detectable marker.
18 . A method of detecting a presence or absence of a CD8, the method comprising:
applying the antigen binding construct of claim 1 to a sample; and
detecting a presence or an absence of the antigen binding construct, thereby detecting a presence of absence of a CD8.
19 . The method of claim 18 , wherein the antigen binding construct is conjugated to a detectable marker.
20 . The method of claim 18 , wherein applying the antigen binding construct comprises administering the antigen binding construct to a subject.
21 . The method of claim 18 , wherein detecting binding or absence of binding of the antigen binding construct to CD8 comprises at least one of positron emission tomography or single-photon emission computed tomography.
22 . The method of claim 18 , the method further comprising applying a secondary antigen binding construct to the sample, wherein the secondary antigen binding construct binds specifically to the antigen binding construct.
23 . The method of claim 18 , wherein the antigen binding construct is incubated with the sample for no more than 20 hours.
24 . The method of claim 18 , wherein the antigen binding construct is incubated with the sample for no more than 6 hours.
25 . The method of claim 18 , wherein the antigen binding construct is administered to a host, and wherein a first quantity of antigen binding construct thereof is unbound to CD8, and a second quantity of antigen binding construct is bound to CD8, wherein at least about 80% of the first quantity of antigen binding construct is eliminated in no more than 12 hours.
26 . A method of targeting a therapeutic agent to a CD8, the method comprising administering to a subject an antigen binding construct of claim 1 , wherein the antigen binding construct is conjugated to a therapeutic agent.