Anti-CD8 antibodies and uses thereof
Anti-CD8 antibodies, radiolabeled anti-CD8 antibodies, fluorescently labeled anti-CD8 antibodies and their use in imaging are provided herein. Included are methods of detecting the presence of CD8 proteins in a subject or sample.
1. A composition comprising:
(i) a radiolabeled antibody conjugate comprising an antibody or antigen binding fragment thereof that binds CD8, a chelating moiety, and a positron emitter, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDRs (HCDR1, HCDR2, and HCDR3) contained within a heavy chain variable region (HCVR) amino acid sequence of SEQ ID NO: 2; and three light chain CDRs (LCDR1, LCDR2, and LCDR3) contained within a light chain variable region (LCVR) amino acid sequence of SEQ ID NO: 10; and
(ii) CD8 expressing T cells.
2. The composition of claim 1 , wherein the positron emitter is 89 Zr.
3. The composition of claim 1 , wherein the chelating moiety is desferrioxamine.
4. The composition of claim 1 , wherein the chelating moiety is
wherein
is a covalent bond to the antibody or antigen-binding fragment thereof.
5. The composition of claim 1 , wherein the radiolabeled antibody conjugate has a chelating moiety to antibody ratio (DAR) of from 1.0 to 2.0.
6. The composition of claim 5 , wherein the chelating moiety-to-antibody ratio is about 1.7.
7. The composition of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 4; an HCDR2 comprising the amino acid sequence of SEQ ID NO: 6; an HCDR3 comprising the amino acid sequence of SEQ ID NO: 8; an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12; an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14; and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.
8. The composition of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an HCVR having an amino acid sequence as set forth in SEQ ID NO: 2 and an LCVR having an amino acid sequence as set forth in SEQ ID NO: 10.
9. A method of identifying a subject for anti-tumor therapy with an anti-PD-1 antibody, or an antigen-binding fragment thereof, or an anti-PD-L1 antibody, or an antigen-binding fragment thereof, comprising:
determining a presence of CD8+ T-cells in a tumor by:
(i) administering a radiolabeled anti-CD8 antibody conjugate to the tumor,
wherein the radiolabeled anti-CD8 antibody conjugate comprises an antibody or antigen-binding fragment thereof that binds CD8, a chelating moiety, and a positron emitter, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDRs (HCDR1, HCDR2, and HCDR3) contained within a heavy chain variable region (HCVR) amino acid sequence of SEQ ID NO: 2; and three light chain CDRs (LCDR1, LCDR2, and LCDR3) contained within a light chain variable region (LCVR) amino acid sequence of SEQ ID NO: 10; and
(ii) visualizing the presence of CD8+ T-cells by positron emission tomography (PET) imaging;
wherein the presence of CD8+ T cells in the tumor identifies the subject for selection for anti-tumor therapy with an anti-PD-1 antibody, or an antigen-binding fragment thereof, or an anti-PD-L1 antibody, or an antigen-binding fragment thereof.
10. The method of claim 9 , wherein the positron emitter is 89 Zr.
11. The method of claim 9 , wherein the chelating moiety is desferrioxamine.
12. The method of claim 9 , wherein the antibody or antigen-binding fragment thereof comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 4; an HCDR2 comprising the amino acid sequence of SEQ ID NO: 6; an HCDR3 comprising the amino acid sequence of SEQ ID NO: 8; an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12; an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14; and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.
13. The method of claim 9 , wherein the antibody or antigen-binding fragment thereof comprises an HCVR having an amino acid sequence as set forth in SEQ ID NO: 2 and an LCVR having an amino acid sequence as set forth in SEQ ID NO: 10.
14. The method of claim 9 , wherein the anti-tumor therapy is an anti-PD-1 antibody or antigen-binding fragment thereof selected from the group consisting of REGN2810, nivolumab, and pembrolizumab.
15. The method of claim 9 , wherein the anti-tumor therapy is an anti-PD-1 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof is REGN2810.
16. The method of claim 9 , wherein the anti-tumor therapy is an anti-PD-L1 antibody or antigen-binding fragment thereof and the anti-PD-L1 antibody or antigen-binding fragment thereof is atezolizumab, avelumab, or durvalumab.
17. The method of claim 9 , wherein the tumor is selected from the group consisting of blood cancer, brain cancer, renal cell cancer, ovarian cancer, bladder cancer, prostate cancer, breast cancer, hepatic cell carcinoma, bone cancer, colon cancer, non-small-cell lung cancer, squamous cell carcinoma of head and neck, colorectal cancer, mesothelioma, B cell lymphoma, and melanoma.
18. A labeling agent comprising:
and wherein Zr is the positron emitter Zr 89 , connected to an anti-CD8 antibody or antigen-binding fragment thereof, wherein the anti-CD8 antibody or antigen-binding fragment thereof is a weak blocker of CD8+ T-cell function, and wherein the antibody or antigen-binding fragment thereof comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 4; an HCDR2 comprising the amino acid sequence of SEQ ID NO: 6; an HCDR3 comprising the amino acid sequence of SEQ ID NO: 8; an LCDR1 comprising the amino acid sequence of SEQ ID NO: 12; an LCDR2 comprising the amino acid sequence of SEQ ID NO: 14; and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.
19. The labeling agent of claim 18 , wherein the antibody or antigen-binding fragment thereof comprises an HCVR having an amino acid sequence as set forth in SEQ ID NO: 2 and an LCVR having an amino acid sequence as set forth in SEQ ID NO: 10.