Anti-HVEM antibodies and use thereof

1 . An antibody or antigen binding fragment thereof comprises three heavy chain CDRs (CDR-H) and three light chain CDRs (CDR-L), wherein: CDR-H1 comprises the amino acid sequence set forth in SEQ ID NO: 1 (SYAMS), CDR-H2 comprises the amino acid sequence as set forth in SEQ ID NO: 2 (AISGSGGSTYYADSVKG), CDR-H3 comprises the amino acid sequence as set forth in SEQ ID NO: 3 (APGDYTAYFDY), CDR-L1 comprises the amino acid sequence as set forth in SEQ ID NO: 4 (RASQSVSSYLA), CDR-L2 comprises the amino acid sequence as set forth in SEQ ID NO: 5 (GASSRAT), and CDR-L3 comprises the amino acid sequence as set forth in SEQ ID NO: 6 (QQYGSSPPYT).

2 . The antibody or antigen binding fragment thereof of claim 1 , comprising a heavy chain comprising the sequence

(SEQ ID NO: 7)

QVQLVQSGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSA

ISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKAP

GDYTAYFDYWGQGTLVTVSS.

3 . The antibody or antigen binding fragment thereof of claim 1 , comprising a light chain comprising the sequence

(SEQ ID NO: 8)

ELVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYG

ASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPPYTFG

QGTKVEIK.

4 . The antibody or antigen binding fragment thereof of claim 1 , comprising a heavy chain comprising the sequence MGWSCIILFLVATATGVHSQVQLVQSGGGLVQPGGSLRLSCAASGFTFSSYA MSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKAPGDYTAYFDYWGQGTLVTVSSASTKGPSVFPLAPCS RSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPR EPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK (SEQ ID NO: 9) and a light chain comprising the sequence

(SEQ ID NO: 10)

MGWSCIILFLVATATGVHSELVLTQSPATLSLSPGERATLSCRASQSVSS

YLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPE

DFAVYYCQQYGSSPPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTA

SVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT

LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC.

5 . A pharmaceutical composition comprising an antibody or antigen binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier, excipient or adjuvant.

6 . A method of treating a disease or condition characterized by HVEM positive cells in a subject in need thereof, the method comprising administering the pharmaceutical composition of claim 5 , thereby treating said disease or condition.

7 . The method of claim 6 , further comprising administering an anti-PD-1/PD-L1 based immunotherapy.

8 . The method of claim 6 , further comprising administering adoptive cell therapy, adoptive tumor infiltrating lymphocyte (TIL) therapy, or a chimeric antigen receptor (CAR) expressing immune cell, wherein said CAR targets a non-HVEM protein on a surface of said HVEM expressing cells.

9 . The method of claim 6 , wherein said disease or condition is an HVEM positive cancer or precancerous lesion.

10 . The method of claim 9 , wherein said HVEM positive cancer is selected from skin cancer, lung cancer and colon cancer.

11 . The method of claim 6 , wherein said disease or condition is an infectious disease and wherein said infected cells comprise HVEM expression.

12 . A method of determining suitability of a subject to be treated by a method of claim 6 , comprising obtaining a disease sample from said subject and determining HVEM levels in said sample, wherein elevated expression of HVEM as compared to a healthy sample or predetermined threshold indicates the subject is suitable for a method of treatment of claim 6 .

13 . A method of detecting HVEM in a sample, the method comprising contacting said sample with an antibody or antigen binding fragment thereof of claim 1 , thereby detecting HVEM.

14 . A kit comprising, the pharmaceutical composition of claim 5 and at least one of:

a. an anti-PD-1/PD-L1 based immunotherapy;

b. a label stating the pharmaceutical composition of the invention is for use with an anti-PD-1/PD-L1 based immunotherapy; and

c. a secondary detection molecule.