Anti-HVEM antibodies
Provided herein are, inter alia, antibodies (e.g. humanized antibodies, monoclonal antibodies, antibody fragments (e.g., scFvs) and antibody compositions (e.g., chimeric antigen receptors, bispecific antibodies), which bind herpesvirus entry mediator (HVEM) with high efficiency and specificity. The antibodies and antibody compositions provided herein include novel light and heavy chain domain CDRs and framework regions and are, inter alia, useful for diagnosing and treating cancer and other HVEM-related diseases.
1 . An anti-Herpes Virus Entry Mediator (HVEM) antibody comprising a light chain variable domain and a heavy chain variable domain, wherein
(a) said light chain variable domain comprises a CDR L1 as set forth in SEQ ID NO:1, a CDR L2 as set forth in SEQ ID NO:2 and a CDR L3 as set forth in SEQ ID NO: 3; and
said heavy chain variable domain comprises a CDR H1 as set forth in SEQ ID NO:4, a CDR H2 as set forth in SEQ ID NO:5, and a CDR H3 as set forth in SEQ ID NO: 6;
(b) said light chain variable domain comprises a CDR L1 as set forth in SEQ ID NO:84, a CDR L2 as set forth in SEQ ID NO:85 and a CDR L3 as set forth in SEQ ID NO: 86; and
said heavy chain variable domain comprises a CDR H1 as set forth in SEQ ID NO: 87, a CDR H2 as set forth in SEQ ID NO:88, and a CDR H3 as set forth in SEQ ID NO: 89; or
(c) said light chain variable domain comprises a CDR L1 as set forth in SEQ ID NO:102, a CDR L2 as set forth in SEQ ID NO:103 and a CDR L3 as set forth in SEQ ID NO:104; and
said heavy chain variable domain comprises a CDR H1 as set forth in SEQ ID NO: 105, a CDR H2 as set forth in SEQ ID NO:106, and a CDR H3 as set forth in SEQ ID NO: 107.
2 . A pharmaceutical composition comprising a therapeutically effective amount of an antibody of claim 1 and a pharmaceutically acceptable excipient.
3 . A method of treating cancer in a subject in need thereof, said method comprising administering to a subject a therapeutically effective amount of an antibody of claim 1 , thereby treating cancer in said subject.
4 . A recombinant protein comprising:
(i) an antibody region comprising a light chain variable domain and a heavy chain variable domain of said antibody of claim 1 ; and
(ii) a transmembrane domain.
5 . A pharmaceutical composition comprising a therapeutically effective amount of a recombinant protein of claim 4 and a pharmaceutically acceptable excipient.
6 . A method of treating cancer in a subject in need thereof, said method comprising administering to a subject a therapeutically effective amount of a recombinant protein of claim 4 , thereby treating cancer in said subject.
7 . A bispecific recombinant protein comprising:
(i) a first antibody region capable of binding an effector cell ligand; and
(ii) a second antibody region, comprising a light chain variable domain and a heavy chain variable domain of said antibody of claim 1 .
8 . A pharmaceutical composition comprising a therapeutically effective amount of a bispecific recombinant protein of claim 7 and a pharmaceutically acceptable excipient.
9 . A method of treating cancer in a subject in need thereof, said method comprising administering to a subject a therapeutically effective amount of a bispecific recombinant protein of claim 8 , thereby treating cancer in said subject.
10 . An anti-Herpes Virus Entry Mediator (HVEM) antibody comprising a light chain variable domain and a heavy chain variable domain,
wherein said light chain variable domain comprises:
a CDR L1 as set forth in SEQ ID NO:66, a CDR L2 as set forth in SEQ ID NO:67 and a CDR L3 as set forth in SEQ ID NO:68; and
wherein said heavy chain variable domain comprises:
a CDR H1 as set forth in SEQ ID NO:69, a CDR H2 as set forth in SEQ ID NO: 70, and a CDR H3 as set forth in SEQ ID NO:71.
11 . An isolated nucleic acid encoding an antibody of claim 10 .
12 . A pharmaceutical composition comprising a therapeutically effective amount of an antibody of claim 10 and a pharmaceutically acceptable excipient.
13 . A method of treating cancer in a subject in need thereof, said method comprising administering to a subject a therapeutically effective amount of an antibody of claim 10 , thereby treating cancer in said subject.
14 . A recombinant protein comprising:
(i) an antibody region comprising a light chain variable domain and a heavy chain variable domain of said antibody of claim 10 ; and
(ii) a transmembrane domain.
15 . A pharmaceutical composition comprising a therapeutically effective amount of a recombinant protein of claim 14 and a pharmaceutically acceptable excipient.
16 . A method of treating cancer in a subject in need thereof, said method comprising administering to a subject a therapeutically effective amount of a recombinant protein of claim 14 , thereby treating cancer in said subject.
17 . A bispecific recombinant protein comprising:
(i) a first antibody region capable of binding an effector cell ligand; and
(ii) a second antibody region, comprising a light chain variable domain and a heavy chain variable domain of said antibody of claim 10 .
18 . A pharmaceutical composition comprising a therapeutically effective amount of a bispecific recombinant protein of claim 17 and a pharmaceutically acceptable excipient.
19 . A method of treating cancer in a subject in need thereof, said method comprising administering to a subject a therapeutically effective amount of a bispecific recombinant protein of claim 18 , thereby treating cancer in said subject.