Anti-idiotypic antibodies to BCMA-targeted binding domains and related compositions and methods
Provided are anti-idiotype antibodies that specifically recognize anti-BCMA antibody moieties, in particular, anti-BC-MA antibody moieties present in recombinant receptors, including chimeric antigen receptors (CARs). The disclosure further relates to uses of antiidiotype antibodies for specifically identifying and/or selecting cells expressing such recombinant receptors, such as anti-BCMA CAR T cells. The disclosure further relates to uses of anti-idiotype antibodies for specifically activating such cells.
1 . An anti-idiotype antibody or antigen-binding fragment thereof that binds to an anti-BCMA target antibody or antigen-binding fragment thereof, wherein the anti-idiotype antibody or antigen-binding fragment comprises:
(a) a VH region comprising a CDR-H1, a CDR-H2, and a CDR-H3, respectively, comprising the CDR-H1, CDR-H2, and CDR-H3 amino acid sequences contained within the amino acid sequence of SEQ ID NO: 114; and
a VL region comprising a CDR-L1, a CDR-L2, and a CDR-L3, respectively, comprising the CDR-L1, CDR-L2, and CDR-L3 amino acid sequences contained within the amino acid sequence of SEQ ID NO: 115.
2 . The anti-idiotype antibody or antigen-binding fragment thereof of claim 1 , wherein:
the VH region comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO: 104, a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO: 105, and a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO: 106; and
the VL region comprises a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO: 111, a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO: 112, and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO: 113.
3 . The anti-idiotype antibody or antigen-binding fragment thereof of claim 2 , wherein the anti-idiotype antibody or antigen-binding fragment thereof comprises:
a heavy chain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 116, and a light chain comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 117.
4 . The anti-idiotype antibody or antigen-binding fragment thereof of claim 2 , wherein the anti-idiotype antibody or antigen-binding fragment thereof comprises
a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 116, and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 117.
5 . The anti-idiotype antibody or antigen-binding fragment thereof of claim 1 , wherein:
the VH region comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 114, and the VL region comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 115.
6 . The anti-idiotype antibody or antigen-binding fragment thereof of claim 1 , wherein:
the VH region comprises the amino acid sequence set forth in SEQ ID NO: 114, and the VL region comprises the amino acid sequence set forth in SEQ ID NO: 115.
7 . The anti-idiotype antibody or antigen-binding fragment thereof of claim 1 , wherein the anti-BCMA target antibody or antigen-binding fragment thereof comprises a VH region comprising the amino acid sequence set forth in SEQ ID NO: 25, and a VL region comprising the amino acid sequence set forth in SEQ ID NO: 26.
8 . The anti-idiotype antibody or antigen-binding fragment thereof of claim 7 , wherein the anti-BCMA target antibody or antigen-binding fragment thereof is a single chain variable fragment (scFv) comprising the amino acid sequence set forth in SEQ ID NO: 27.
9 . The anti-idiotype antibody or antigen-binding fragment thereof of claim 1 , wherein
the anti-idiotype antibody or antigen-binding fragment binds the anti-BCMA target antibody or antigen-binding fragment comprised within or included in an antigen-binding domain of an extracellular portion of a CAR.
10 . The anti-idiotype antibody or antigen-binding fragment thereof of claim 1 , wherein:
the anti-idiotype antibody or antigen-binding fragment thereof is an agonist of a CAR comprising the anti-BCMA target antibody or antigen-binding fragment thereof.
11 . The anti-idiotype antibody or antigen-binding fragment thereof of claim 1 , wherein binding of the anti-idiotype antibody or antigen-binding fragment thereof to the anti-BCMA target antibody or antigen-binding fragment thereof is not blocked by human BCMA or human BCMA-Fc.
12 . A conjugate, comprising the anti-idiotype antibody or antigen-binding fragment thereof of claim 1 and a heterologous molecule or moiety.
13 . A composition comprising the anti-idiotype antibody or antigen-binding fragment thereof of claim 1 or a conjugate comprising the anti-idiotype antibody or antigen-binding fragment thereof of claim 1 and a heterologous molecule or moiety.
14 . A nucleic acid molecule(s) encoding the heavy chain and/or the light chain of the anti-idiotype antibody or antigen-binding fragment thereof of claim 1 .
15 . A vector, comprising the nucleic acid molecule(s) of claim 14 .
16 . A cell, comprising the nucleic acid molecule of claim 14 .
17 . A method of producing an anti-idiotype antibody or antigen-binding fragment thereof, comprising expressing the heavy and/or light chain encoded by the nucleic acid molecule(s) of claim 14 in a suitable host cell and recovering or isolating the antibody.
18 . A method of detecting a target antibody or antigen-binding fragment thereof, comprising:
(a) contacting a composition comprising a target antibody or antigen-binding fragment thereof with the anti-idiotype antibody or antigen-binding fragment thereof of claim 1 or a conjugate comprising the anti-idiotype antibody or antigen-binding fragment thereof of claim 1 and a heterologous molecule or moiety, wherein the anti-idiotype antibody or antigen-binding fragment thereof specifically binds to the target antibody or antigen-binding fragment thereof; and
(b) detecting the anti-idiotype antibody bound to the target antibody or antigen-binding fragment thereof.
19 . The method of claim 18 , wherein the target antibody or antigen-binding fragment thereof is bound to a cell or expressed on the surface of a cell and the detecting in (b) comprises detecting cells bound with the anti-idiotype antibody or antigen-binding fragment thereof, and wherein the cell expresses on its surface a CAR comprising the target antibody or antigen-binding fragment thereof.
20 . A method of selecting cells from a cell population, comprising:
(a) contacting a cell population expressing a CAR comprising a target antibody or antigen-binding fragment thereof or a cell bound to a target antibody or antigen-binding fragment thereof with the anti-idiotype antibody or antigen-binding fragment thereof of claim 1 , or a conjugate comprising the anti-idiotype antibody or antigen-binding fragment thereof of claim 1 and a heterologous molecule or moiety, wherein the anti-idiotype antibody or antigen-binding fragment thereof specifically binds to the target antibody or antigen-binding fragment thereof; and
(b) selecting cells bound with the anti-idiotype antibody or antigen-binding fragment thereof.