ANTIBODIES AND METHODS OF USE THEREOF
Disclosed herein are methods and compositions for targeting a complex comprising a neoantigen presenting protein and a neoantigen in cancer. Further disclosed herein are antibodies that selectively bind to a complex comprising a neoantigen presenting protein and a neoantigen, as well as methods of use thereof.
1 . A method of treating a cancer characterized by the presence of a plurality of cancer cells that differentially express a neoantigen presenting protein and a neoantigen, the method comprising contacting the cells with an antibody that selectively binds to both the neoantigen presenting protein and the neoantigen in a complex comprising the neoantigen presenting protein and the neoantigen, thereby treating the cancer.
2 . The method of claim 1 , wherein the antibody does not have a binding affinity to (i) the neoantigen presenting protein alone; or (ii) the neoantigen alone.
3 . The method of claim 1 , wherein the neoantigen comprises, consists essentially of, or consists of a sequence according to SEQ ID NO: 3 (VMAPRTLFL), SEQ ID NO: 13 (VMAPRTLIL), SEQ ID NO: 14 (VMPPRTLLL), SEQ ID NO: 31 (VMAPRTLVL), SEQ ID NO: 19 (YLLPRRGPRL), SEQ ID NO: 20 (AISPRTLNA), SEQ ID NO: 21 (SQAPLPCVL), SEQ ID NO: 15 (YLLEMLWRL), SEQ ID NO: 16 (YMLDLQPETT), SEQ ID NO: 22 (QMRPVSRVL), SEQ ID NO: 23 (ALALVRMLI), SEQ ID NO: 24 (SQQPYLQLQ), SEQ ID NO: 25 (AMAPIKTHL), SEQ ID NO: 26 (AMAPIKVRL), SEQ ID NO: 17 (YLLPAIVHI), SEQ ID NO: 27 (ILDQKINEV), SEQ ID NO: 28 (GVYDGEEHSV), SEQ ID NO: 29 (KVLEYVIKV), SEQ ID NO: 18 (SLLMWITQV), SEQ ID NO: 30 (YLEPGPVTV), SEQ ID NO: 32 (SLLEKSLGL), SEQ ID NO: 22 (QMRPVSRVL), SEQ ID NO: 33 (WIAAVTIAA), SEQ ID NO: 34 (TSDMPGTTL), SEQ ID NO: 35 (MLALLTQVA), SEQ ID NO: 36 (QMFEGPLAL), SEQ ID NO: 37 (VLWDRTFSL), SEQ ID NO: 38 (TLFFQQNAL), SEQ ID NO: 1 (GLADKVYFL), or SEQ ID NO: 2 (ILSPTVVSI).
4 . The method of claim 1 , wherein the antibody is a camelid single domain antibody.
5 . The method of claim 1 , wherein the antibody is a multispecific antibody.
6 . The method of claim 1 , wherein the antibody is a multifunctional antibody.
7 . The method of claim 1 , wherein the binding of the antibody to the complex induces an immune response against the cancer cell.
8 . The method of claim 1 , wherein the antibody further comprises a conjugated therapeutic moiety.
9 . The method of claim 8 , wherein the therapeutic moiety kills the cancer cell.