Antibodies and antigen binding fragments against CD155 methods of use thereof
A humanized antibody or antigen binding fragment that binds to the poliovirus receptor (PVR) can be utilized in the preparation of antibody drug conjugates (ADCs) to target nucleic acids, peptides and proteins, drugs and radiopharmaceuticals to cancer cells. These antibodies or antigen binding fragments can also be used for checkpoint blockade. The humanized antibody or antigen binding fragment of this invention can also modulate the PVR-DNAM-1 axis in order to upregulate DNAM 1 (CD226) expression on T cells or NK cells. The antibody or antigen binding fragment that bind to PVR can also be incorporated in CAR-T cells or CAR-NK cells. Bispecific antibodies can also be produced by incorporating the anti-CD155 antibodies or antigen binding fragments to engage T cells or NK cells to fight cancers that express CD155.
1 . A monoclonal antibody or antigen binding fragment against the poliovirus receptor (CD155) comprising:
(a) a heavy chain variable region selected from the group consisting of SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26 and
(b) a light chain variable region selected from the group consisting of SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22 or SEQ ID NO: 23.
2 . The monoclonal antibody or antigen binding fragment of claim 1 conjugated to a prodrug or a drug administered to a human for the treatment of tumors expressing CD155.
3 . The monoclonal antibody or antigen binding fragment of claim 2 , wherein the drug or prodrug is selected from one of the following: a nucleic acid, vedotin, a pyrrolobenzodiazepine, liposomal doxorubicin, a topoisomerase inhibitor, MMAE, MMAF, DM1, paclitaxel, temozolomide, doxorubicin, trastuzumab deruxtecan, a radiosensitizing drug, tesirine, docetaxel and a PARP inhibitor.
4 . The monoclonal antibody or antigen binding fragment of claim 1 , wherein the monoclonal antibody or antigen binding fragment binds CD155 and blocks the binding of CD155 to TIGIT.
5 . The monoclonal antibody or antigen binding fragment of claim 1 , wherein the monoclonal antibody or antigen binding fragment binds CD155 and blocks the binding of CD155 to CD96.
6 . The monoclonal antibody or antigen binding fragment of claim 1 comprising a bispecific monoclonal antibody or antigen binding fragment including a first part that binds CD155 and a second part that binds at least one of the following: (a) CD3 on T cells and (b) NKp46 on NK cells.
7 . The monoclonal antibody or antigen binding fragment of claim 1 comprising a bispecific monoclonal antibody or antigen binding fragment including a first part that binds CD155 and a second part that binds at least one of the following: (a) transferrin receptor 1 and (b) transferrin receptor 2.
8 . The monoclonal antibody or antigen binding fragment of claim 1 comprising a bispecific monoclonal antibody or antigen binding fragment including a first part that binds the poliovirus receptor and a second part that binds Type 1 insulin-like growth factor receptor.
9 . The monoclonal antibody or antigen binding fragment of claim 1 comprising a bispecific monoclonal antibody or antigen binding fragment including a first part that binds the poliovirus receptor and a second part comprising single domain antibody FC5.
10 . The monoclonal antibody or antigen binding fragment of claim 1 , wherein the monoclonal antibody or antigen binding fragment binds to CD155 in non-human primates.
11 . The monoclonal antibody or antigen binding fragment of claim 1 with an IgG1 isotype where the monoclonal antibody or antigen binding fragment binds to CD155 expressed on a tumor and elicits an immune response against the tumor through ADCC or CDC.
12 . The monoclonal antibody or antigen binding fragment of claim 1 , wherein the monoclonal antibody or antigen binding fragment binds CD155 followed by an elevation of DNAM 1 on at least one of the following (a) T cells and (b) NK cells.
13 . The monoclonal antibody or antigen binding fragment of claim 1 , wherein the monoclonal antibody or antigen binding fragment against CD155 is administered to a human and the monoclonal antibody or antigen binding fragment binds to CD155 in the human and blocks poliovirus from binding to CD155.
14 . The monoclonal antibody or antigen binding fragment of claim 1 , wherein the monoclonal antibody or antigen binding fragment against CD155 is administered to a human for the treatment of cancer in combination with an antibody against an immune checkpoint molecule selected from the group consisting of CTLA-4, PD-1 PD-L1, CD112R, OX40, TIGIT, NKG2A, CEACAM1, B7-H3, B7-H4, VISTA, LAG-3, CD137, KIR, TIM-1, TIM-3, LAIR1, HVEM, BTLA, CD160, CD200, CD200R, and A2aR.
15 . The monoclonal antibody or antigen binding fragment of claim 1 , where in the monoclonal antibody or antigen binding fragment comprises an IgG4 isotype with a S241P hinge mutation.
16 . The monoclonal antibody or antigen binding fragment of claim 1 , wherein the monoclonal antibody or antigen binding fragment against CD155 comprises a label selected from one of the following: (a) 1-124, (b) Gallium 68, (c) Lutetium 177, (d) a contrast agent for CT scan, (e) a contrast agent for MRI scan and (f) a diagnostic agent for PET scan.
17 . The monoclonal antibody or antigen binding fragment of claim 1 , where the monoclonal antibody or antigen binding fragment against CD155 is conjugated to a mRNA encoding one of the following mRNA for a cytokine or a gene editing enzyme: (a) mRNA encoding IL-2, (b) mRNA encoding IL-7, (c) mRNA encoding IL-12, (d) mRNA encoding IL-15, (e) mRNA encoding IL-21, (f) mRNA encoding IFN gamma, (g) mRNA encoding IFN alpha, (h) mRNA encoding GM-CSF, (i) mRNA encoding Cas9, (j) mRNA encoding Cas12a and (k) mRNA encoding Cas13.
18 . The monoclonal antibody or antigen binding fragment of claim 1 administered by at least one of the administration routes selected from the group consisting of intravenously, intra-arterially, intratumorally, intrathecally, intramuscularly, subcutaneously, intravascularly, intraperitoneally, and via convection-enhanced delivery.
19 . A cell line that produces the monoclonal antibody or antigen binding fragment against the poliovirus receptor (CD155) comprised of a heavy chain variable region and a light chain variable region from the following:
(a) a heavy chain variable region selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26 and
(b) a light chain variable region selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22 or SEQ ID NO: 23.