Methods and compositions relating to anti-PD1 antibody reagents
Described herein are novel anti-PD1 antibody reagents (e.g., antibodies, antigen-binding fragments thereof, and/or chimeric antigen receptors). Also described herein antibody-drug conjugates or kits comprising the disclosed antibody reagents, as well as methods of treating cancer by administering the disclosed antibody reagents.
1. An antibody, antibody reagent, antigen-binding fragment thereof, or chimaeric antigen receptor (CAR), that specifically binds an PD1 polypeptide, said antibody reagent, antigen-binding portion thereof, or CAR comprising:
heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 23-25 and light chain CDRs having the amino acid sequences of SEQ ID NOs: 26-28; or
heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 29-31 and light chain CDRs having the amino acid sequences of SEQ ID NOs: 32-34; or
heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 35-37 and light chain CDRs having the amino acid sequences of SEQ ID NOs: 38-40; or
heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 41-43 and light chain CDRs having the amino acid sequences of SEQ ID NOs: 44-46; or
heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 47-49 and light chain CDRs having the amino acid sequences of SEQ ID NOs: 50-52; or
heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 53-55 and light chain CDRs having the amino acid sequences of SEQ ID NOs: 56-58; or
heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 59-61 and light chain CDRs having the amino acid sequences of SEQ ID NOs: 62-64; or
heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 65-67 and light chain CDRs having the amino acid sequences of SEQ ID NOs: 68-70; or
heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 71-73 and light chain CDRs having the amino acid sequences of SEQ ID NOs: 74-76; or
heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 77-79 and light chain CDRs having the amino acid sequences of SEQ ID NOs: 80-82; or
heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 83-85 and light chain CDRs having the amino acid sequences of SEQ ID NOs: 86-88.
2. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , comprising the heavy chain sequence of any of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 or 21.
3. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , comprising the light chain sequence of any of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, or 22.
4. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , comprising:
the heavy chain sequence of SEQ ID NO: 1 and the light chain sequence of SEQ ID NO: 2; or
the heavy chain sequence of SEQ ID NO: 3 and the light chain sequence of SEQ ID NO: 4; or
the heavy chain sequence of SEQ ID NO: 5 and the light chain sequence of SEQ ID NO: 6; or
the heavy chain sequence of SEQ ID NO: 7 and the light chain sequence of SEQ ID NO: 8; or
the heavy chain sequence of SEQ ID NO: 9 and the light chain sequence of SEQ ID NO: 10; or
the heavy chain sequence of SEQ ID NO: 11 and the light chain sequence of SEQ ID NO: 12; or
the heavy chain sequence of SEQ ID NO: 13 and the light chain sequence of SEQ ID NO: 14; or
the heavy chain sequence of SEQ ID NO: 15 and the light chain sequence of SEQ ID NO: 16; or
the heavy chain sequence of SEQ ID NO: 17 and the light chain sequence of SEQ ID NO: 18; or
the heavy chain sequence of SEQ ID NO: 19 and the light chain sequence of SEQ ID NO: 20; or
the heavy chain sequence of SEQ ID NO: 21 and the light chain sequence of SEQ ID NO: 22.
5. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 4 , further comprising a conservative substitution in a sequence not comprised by a CDR.
6. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , wherein the antibody reagent or antigen-binding fragment thereof is fully human or fully humanized.
7. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , wherein the antibody reagent or antigen-binding fragment thereof is fully humanized except for the CDR sequences.
8. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , wherein the reagent or fragment is selected from the group consisting of:
an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR-grafted antibody, a humanized antibody, a Fab, a Fab′, a F(ab′)2, a Fv, a disulfide linked Fv, a scFv, a single domain antibody, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, and a bispecific antibody.
9. A composition comprising the antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , and a chemotherapeutic agent.
10. The composition of claim 9 , wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR is conjugated to the chemotherapeutic agent.
11. A method of treating cancer in a subject in need thereof, the method comprising administering the antibody, antibody reagent, antigen-binding fragment thereof, or CAR of claim 1 to the subject.
12. The method of claim 11 , wherein the cancer is selected from the group consisting of:
Non-small cell lung cancer; melanoma; metastatic melanoma; renal cell carcinoma; squamous cell carcinoma of the head and neck; Hodgkin lymphoma; classical Hodgkin lymphoma; and urothelial carcinoma.