Granted Patent B2

US 10,201,606 · App. 14/952,448 · Granted Feb 12, 2019

Abstract

Claims (21)

1. A method of immunotherapy of a patient in need thereof, comprising:

(a) administering to the patient a population of immune effector cells that express on their surface a recombinant antigen-recognizing receptor that specifically binds human CD20 antigen, wherein the CD20 antigen is expressed on target cells in the patient and on at least one type of non-target hematopoietic cells in the patient; and

(b) administering to the patient a population of hematopoietic cells, a plurality of which have been recombinantly altered to express a human CD20 antigen in a form that has been altered to include one or more amino acid deletions or substitutions in SEQ. ID NO:3 such that the antigen-recognizing receptor on the immune effector cells has an affinity for the altered CD20 antigen that is at least 10-fold less than its affinity for the native CD20 antigen.

2. The method of claim 1 , wherein

the antigen-recognizing receptor on the immune effector cells has an affinity for the altered CD20 antigen that is 1000-fold to 100,000-fold less than its affinity for the native CD20 antigen.

3. The method of claim 1 , wherein the antigen-recognizing receptor is a chimeric antigen receptor (CAR) comprising an antibody variable region specific for the CD20 antigen in tandem with a T cell stimulatory domain.

4. The method of

claim 2 , wherein the T cell stimulatory domain is a CD3ξ domain.

5. The method of claim 1 , wherein the patient is concurrently administered with both the population of immune effector cells and the population of hematopoietic cells.

6. The method of claim 1 , wherein the hematopoietic cells are hematopoietic stem cells or hematopoietic progenitor cells.

7. The method of claim 1 , wherein the immune effector cells and the hematopoietic cells are both autologous to the patient.

8. The method of claim 3 , wherein the CAR comprises SEQ. ID NO:1 (V H ) and SEQ. ID NO:2 (V L ).

9. The method of claim 1 , wherein

the hematopoietic cells express a splice variant of CD20 that the antigen-recognizing receptor on the immune effector cells does not bind.

10. The method of claim 1 , wherein the form of CD20 expressed by the hematopoietic cells comprises SEQ. ID NO:3 with an amino acid substitution at position 170 and/or position 172.

11. The method of claim 1 , wherein the target cells are a type of hematopoietic cell that expresses the CD20 antigen.

12. A method of reducing the side effects of immunotherapy against antigen-expressing non-target cells in a patient,

wherein the immunotherapy comprises administering to the patient a population of immune effector cells that express a chimeric antigen receptor (CAR), wherein the CAR comprises an antibody variable region that is specific for CD20 antigen expressed by target cells in the patient, in tandem with a T cell signaling domain;

wherein the method of reducing side effects comprises:

(a) obtaining a pharmaceutical composition comprising a population of hematopoietic cells that express the same antigen that is expressed by the target cells, but in a form that has been recombinantly altered to include one or more amino acid deletions or substitutions in SEQ. ID NO:3 that inhibit binding of the altered CD20 by the CAR; and

(b) administering the hematopoietic cells to the patient before, during, or after administration of the immune effector cells.

Assignments (2)

Cited By (9)

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