Anti-idiotype antibodies targeting anti-CD70 chimeric antigen receptor

Patent metadata

Field	Value
Publication number	US-11795238-B2
Application number	US-202117392740-A
Country	US
Kind code	B2
Filing date	Aug 3, 2021
Priority date	Aug 4, 2020
Publication date	Oct 24, 2023
Grant date	Oct 24, 2023

Abstract

High affinity antibodies capable of binding to a single-chain variable fragment (scFv) of anti-CD70 antibody, for example, the scFv expressed on cell surface as a portion of a chimeric antigen receptor (CAR). Also provided herein are methods for producing such anti-scFv antibodies and methods of using the antibodies disclosed herein for detecting, for example, T cells expressing an anti-CD70 CAR that comprise the scFv as an extracellular domain.

First claim

What is claimed is:

1. An isolated antibody, which binds a single-chain variable fragment (scFv) consisting of the amino acid sequence of SEQ ID NO: 1, wherein the antibody comprises heavy chain complementary determining region (CDR)1, CDR2, and CDR3 comprising the amino acid sequences of SEQ ID NOs:9-11, respectively, and light chain CDR1, CDR2, and CDR3 comprising the amino acid sequences SEQ ID NOs:15-17, respectively, following the Kabat approach.

2. The isolated antibody of claim 1 , wherein the antibody binds the scFv expressed on a cell surface.

3. The isolated antibody of claim 1 , which comprises a heavy chain variable region (V H ) comprising the amino acid sequence of SEQ ID NO:2 and a light chain variable region (V L ) comprising the amino acid sequence of SEQ ID NO:3.

4. The isolated antibody of claim 1 , wherein the antibody is a full-length antibody or an antigen-binding fragment thereof.

5. The isolated antibody of claim 3 , which comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:22 and a light chain comprising the amino acid sequence of SEQ ID NO:23.

6. A method for detecting or quantifying a single-chain variable fragment (scFv) that consists of the amino acid sequence of SEQ ID NO: 1 in a sample, the method comprising:
(i) contacting an antibody of claim 1 with a sample suspected of containing the scFv, and
(ii) detecting binding of the antibody to the scFv, wherein the scFv is the extracellular domain of an anti-CD70 chimeric antigen receptor (CAR) expressed on a cell surface.

7. The method of claim 6 , wherein the antibody is conjugated to a detectable label.

8. The method of claim 6 , wherein the antibody is conjugated to biotin.

9. The method of claim 6 , wherein step (ii) comprises a secondary antibody.

10. The method of claim 6 , wherein the sample comprises a plurality of T cells, which are genetically engineered to express the anti-CD70 CAR.

11. The method of claim 10 , wherein the plurality of T cells are prepared from T cells obtained from one or more donors.

12. The method of claim 10 , wherein the sample is obtained from a process for producing a plurality of T cells, which are genetically engineered to express the anti-CD70 CAR.

13. The method of claim 10 , wherein the sample is a biological sample obtained from a subject administered a plurality of T cells, which are genetically engineered to express the anti-CD70 CAR.

14. The method of claim 13 , wherein the biological sample is a blood sample or a tissue sample.

15. The method of claim 13 , wherein the subject is a human cancer patient.

16. The method of claim 15 , wherein the human cancer patient has a relapsed or refractory B-cell malignancy.

17. The method of claim 16 , wherein the relapsed or refractory B-cell malignancy is non-Hodgkin lymphoma or B-cell lymphoma.

18. The method of claim 17 , wherein the human cancer patient has a CD70+ solid tumor.

19. The method of claim 18 , wherein the CD70+ solid tumor is a renal cell carcinoma (RCC), a lung cancer, a gastric cancer, an ovarian cancer, a pancreatic cancer, a prostate cancer, and/or a combination thereof.

20. The method of claim 9 , wherein the plurality of T cells comprise a disrupted TRAC gene, a disrupted β2M gene, or both.

Assignees

• Crispr Therapeutics Ag

Inventors

• Kumar Lalit
• Dequeant Mary-Lee

Classifications

• C07K16/4266 Primary

  against anti-tumor receptor Ig · CPC title

• G01N33/6854

  Immunoglobulins · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• G01N2333/70575

  NGF/TNF-superfamily, e.g. CD70, CD95L, CD153 or CD154 · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title