Anti-B7-H3 monoclonal antibody and methods of use thereof
Provided herein are agents, such as antibodies, antibody-drug conjugates, or chimeric antigen receptors, that target B7-H3. Methods of treating cancer are provided, comprising administering to a patient in need thereof an effective amount of an B7-H3-targeting agent. The patient may be selected for treatment if the cancer expresses an increased level of B7-H3.
1 . A monoclonal antibody or antibody fragment, wherein the antibody or antibody fragment comprises a heavy chain variable region (VH) comprising VHCDR1, VHCDR2, and VHCDR3 amino acid sequences from SEQ ID NO: 7; and a light chain variable region (VL) comprising VLCDR1, VLCDR2, and VLCDR3 amino acid sequences from SEQ ID NO: 8; and wherein the antibody is capable of binding to B7-H3.
2 . The monoclonal antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment comprises;
(a) a heavy chain variable region (VH) having a VHCDR1 amino acid sequence comprising SEQ ID NO: 1, a VHCDR2 amino acid sequence comprising SEQ ID NO: 2, and a VHCDR3 amino acid sequence comprising SEQ ID NO: 3; and a light chain variable region (VL) having a VLCDR1 amino acid sequence comprising SEQ ID NO: 4, a VLCDR2 amino acid sequence comprising SEQ ID NO: 5, and a VLCDR3 amino acid sequence comprising SEQ ID NO: 6;
(b) a heavy chain variable region (VH) having a VHCDR1 amino acid sequence comprising SEQ ID NO: 11, a VHCDR2 amino acid sequence comprising SEQ ID NO: 12, and a VHCDR3 amino acid sequence comprising SEQ ID NO: 13; and a light chain variable region (VL) having a VLCDR1 amino acid sequence comprising SEQ ID NO: 14, a VLCDR2 amino acid sequence comprising SEQ ID NO: 15, and a VLCDR3 amino acid sequence comprising SEQ ID NO: 16;
(c) a heavy chain variable region (VH) having a VHCDR1 amino acid sequence comprising SEQ ID NO: 17, a VHCDR2 amino acid sequence comprising SEQ ID NO: 18, and a VHCDR3 amino acid sequence comprising SEQ ID NO: 19; and a light chain variable region (VL) having a VLCDR1 amino acid sequence comprising SEQ ID NO: 20, a VLCDR2 amino acid sequence comprising SEQ ID NO: 21, and a VLCDR3 amino acid sequence comprising SEQ ID NO: 6; or
(d) a heavy chain variable region (VH) having a VHCDR1 amino acid sequence comprising SEQ ID NO: 17, a VHCDR2 amino acid sequence comprising SEQ ID NO: 18, and a VHCDR3 amino acid sequence comprising SEQ ID NO: 19; and a light chain variable region (VL) having a VLCDR1 amino acid sequence comprising SEQ ID NO: 4, a VLCDR2 amino acid sequence comprising SEQ ID NO: 5, and a VLCDR3 amino acid sequence comprising SEQ ID NO: 6.
3 . The monoclonal antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment comprises a heavy chain variable sequence having at least 95% identity to SEQ ID NO: 7 and a light chain variable sequence having at least 95% identity to SEQ ID NO: 8.
4 . The monoclonal antibody or antibody fragment of claim 1 , wherein said antibody or antibody fragment is a humanized antibody.
5 . The monoclonal antibody or antibody fragment of claim 1 , wherein the antibody fragment is a monovalent scFv (single chain fragment variable) antibody, divalent scFv, Fab fragment, F(ab′) 2 fragment, Fv fragment, or single chain antibody.
6 . The monoclonal antibody or antibody fragment of claim 1 , wherein said antibody is a chimeric antibody, bispecific antibody, IgG antibody, or recombinant IgG antibody.
7 . The monoclonal antibody or antibody fragment of claim 1 , wherein the antibody is conjugated or fused to an imaging agent, a cytotoxic agent, a metal, or a radioactive moiety.
8 . The monoclonal antibody or antibody fragment of claim 7 , wherein the imaging agent is a fluorophore.
9 . The monoclonal antibody or antibody fragment of claim 7 , wherein the radioactive moiety is Zr-89, Cu-64, F-18, Y-90, Lu-177, At-211, Ac-225, or Pb-212.
10 . The monoclonal antibody or antibody fragment of claim 1 , wherein the antibody is an immune conjugate.
11 . The monoclonal antibody or antibody fragment of claim 1 , wherein the antibody is an antibody-drug conjugate.
12 . An isolated nucleic acid encoding the antibody heavy and/or light chain variable region of the antibody molecule of claim 1 .
13 . An engineered cell comprising a vector comprising a nucleic acid encoding an antibody or antibody fragment of claim 1 .
14 . A method of making a monoclonal antibody or antibody fragment comprising culturing the engineered cell of claim 13 under conditions that allow expression of the antibody.
15 . A pharmaceutical formulation comprising the antibody or antibody fragment of claim 1 .
16 . A method of treating a patient having a cancer, the method comprising that expresses B7-H3 administering an effective amount of antibody or antibody fragment of claim 1 .
17 . A method for detecting the presence of B7-H3 on the surface of a cell, in a tissue, in an organ, or an in a biological sample, the method comprising (a) contacting the cell, tissue, organ, or biological sample with an antibody of claim 1 ; and (b) detecting the presence of the antibody associated with the cell, tissue, organ, or sample.