Methods and compositions for adoptive cell therapy

Patent metadata

Field	Value
Publication number	US-11266739-B2
Application number	US-201514958919-A
Country	US
Kind code	B2
Filing date	Dec 3, 2015
Priority date	Dec 3, 2014
Publication date	Mar 8, 2022
Grant date	Mar 8, 2022

Abstract

Provided are methods for multiple administrations of cells for adoptive cell therapy, and for administering cells to subjects having received prior administrations, and compositions and articles of manufacture for use in the methods. The cells generally express recombinant molecules such as recombinant receptors, e.g., chimeric antigen receptors (CARs) and/or other transgenic receptors. The methods can involve administering cells expressing a first or prior receptor(s) and cells expressing a second or subsequent receptor(s), the second or subsequent receptor(s) being distinct from the first, and which generally do not express the first receptor, and/or administering the cells expressing the second receptor to a subject having received the first administration. The methods can provide various advantages, such as improved efficacy in the context an immune response in the subject against the first or prior receptor and/or in the context of antigen loss, downregulation, or modification, following a first or prior administration.

First claim

The invention claimed is:

1. A method of treatment, comprising:
(a) administering to a subject T cells expressing a first chimeric antigen receptor (CAR) that specifically binds to a first antigen associated with a disease or condition in the subject, wherein the disease or condition comprises a B cell acute lymphoblastic leukemia (B-ALL) and the first antigen is CD19; and
(b) subsequently administering, to a subject in which the disease or condition has relapsed following the administration of the first CAR in (a), T cells expressing a second CAR that specifically binds to a second antigen that is CD22, wherein:
at the time of, or immediately prior to, the administration of T cells expressing the second CAR, the subject is in the relapse following the administration of T cells expressing the first CAR; and
the T cells expressing the second CAR do not express the first CAR, and the second CAR comprises at least one region identical in amino acid sequence to a corresponding region of the first CAR.

2. A method of treatment, comprising administering T cells expressing a second chimeric antigen receptor (CAR) to a subject that has previously received an administration of T cells expressing a first chimeric antigen receptor (CAR) and has relapsed following the previous administration of the first CAR, wherein:
said T cells expressing the second CAR do not express the first CAR;
said first CAR specifically binds to a first antigen associated with a disease or condition in the subject, wherein the disease or condition comprises a B cell acute lymphoblastic leukemia (B-ALL) and the first antigen is CD19;
said second CAR specifically binds to a second antigen that is CD22, and said second CAR comprises at least one region identical in amino acid sequence to a corresponding region of said first CAR; and
at the time of, or immediately prior to, the administration of T cells expressing the second CAR, the subject is in the relapse following the administration of T cells expressing the first CAR.

3. The method of claim 1 , wherein:
the time between the initiation of administration of T cells expressing the first CAR and the initiation of administration of T cells expressing the second CAR is at least about 28 days, at least about 35 days, at least about 42 days, at least about 49 days, or at least about 60 days.

4. The method of claim 2 , wherein:
the time between initiation of the administration of T cells expressing the first CAR and initiation of the administration of T cells expressing the second CAR is at least about 28 days, at least about 35 days, at least about 42 days, at least about 49 days, or at least about 60 days.

5. The method of claim 2 , wherein said subject has not received a dose of T cells expressing the second CAR prior to the administration of cells expressing the second CAR.

6. The method of claim 2 , wherein:
the administration of the T cells expressing the second CAR comprises administration of the cells in an amount sufficient for reduction in burden of the disease or condition in the subject; or
the administration of the T cells expressing the second CAR effects a reduction in burden of the disease or condition in the subject, thereby treating the disease or condition.

7. The method of claim 2 , wherein:
the administration of the T cells expressing the first CAR comprises administration of the cells in an amount sufficient for reduction in burden of the disease or condition in the subject; or
the administration of the T cells expressing the first CAR and/or the administration of the cells expressing the second CAR effects a reduction in burden of the disease or condition in the subject, thereby treating the disease or condition.

8. The method of claim 2 , wherein the T cells expressing the second CAR are autologous to the subject.

9. The method of claim 2 , wherein the administration of the T cells expressing the first CAR and/or the administration of the T cells expressing the second CAR independently comprises administration of from or from about 1×10 6 to about 1×10 8 of the CAR-expressing T cells.

10. The method of claim 2 , wherein administration of the T cells expressing the second CAR comprise administration of from or from about 1×10 6 to about 1×10 8 of the CAR-expressing T cells.

11. The method of claim 2 , wherein the T cells expressing the first CAR are autologous to the subject.

12. The method of claim 1 , wherein the T cells expressing the first CAR and the T cells expressing the second CAR are autologous to the subject.

13. The method of 1 , wherein the administration of the T cells expressing the first CAR and/or the administration of the T cells expressing the second CAR independently comprises administration of from or from about 1×10 6 to about 1×10 8 of the CAR-expressing T cells.

14. The method of claim 1 , wherein administration of the T cells expressing the second CAR comprise administration of from or from about 1×10 6 to about 1×10 8 of the CAR-expressing T cells.

15. The method of claim 2 , wherein said subject has not received a dose of T cells expressing a CAR that binds to the second antigen prior to the administration of T cells expressing the second CAR.

16. A method of treatment, comprising:
(a) administering, to a subject having a disease or condition that is a B cell malignancy, T cells expressing a first chimeric antigen receptor (CAR) that specifically binds to a first antigen that is CD19; and
(b) subsequently administering, to a subject in which the disease or condition has relapsed following the administration of the first CAR in (a), T cells expressing a second CAR that specifically binds to a second antigen that is CD22, wherein the T cells expressing the second CAR do not express the first CAR, and the second CAR comprises at least one region identical in amino acid sequence to a corresponding region of the first CAR, wherein:
at the time of, or immediately prior to, initiation of the administration of T cells expressing the second CAR, the subject is in the relapse following the administration of T cells expressing the first CAR.

17. The method of claim 16 , wherein the disease or condition is a leukemia or a lymphoma.

18. The method of claim 16 , wherein the T cells expressing the first CAR and the T cells expressing the second CAR are autologous to the subject.

19. The method of claim 16 , wherein the administration of the T cells expressing the first CAR and/or the administration of the cells expressing the second CAR independently comprises administration of from or from about 1×10 6 to about 1×10 8 of the CAR-expressing T cells.

20. The method of claim 16 , wherein the time between the initiation of administration of the T cells expressing the first CAR and the initiation of administration of the T cells expressing the second CAR is at least about 28 days, at least about 35 days, at least about 42 days, at least about 49 days, or at least about 60 days.

21. A method of treatment, comprising administering, to a subject having a disease or condition that is a B cell malignancy, T cells expressing a second chimeric antigen receptor (CAR), wherein:
the subject has previously received an administration of T cells expressing a first chimeric antigen receptor (CAR) that specifically binds to a first antigen that is CD19 and has relapsed following the previous administration of the first CAR;
the second CAR specifically binds to a second antigen that is CD22, wherein the T cells expressing the second CAR do not express

Assignees

• Juno Therapeutics Inc

Inventors

• Gilbert Mark J

Classifications

• C07K14/7051 Primary

  T-cell receptor (TcR)-CD3 complex · CPC title

• C07K2319/02

  containing a signal sequence · CPC title

• A61K2239/48

  Blood cells, e.g. leukemia or lymphoma · CPC title

• A61K2239/13

  Antibody-based · CPC title

• A61K2239/38

  characterised by the dose, timing or administration schedule · CPC title