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US 5,595,721 AGranted
Radioimmunotherapy of lymphoma using anti-CD20
AssigneeCoulter Pharmaceutical, Inc.
InventorsMark S. Kaminski, Gregory M. Butchko, Stephan D. Glenn, Richard L. Wahl
Life of this patent
Estimating the term…
Abstract
Methods for the treatment of lymphoma by adminstration of a B cell-specific antibody are described. The invention encompasses providing to a patient both unlabeled antibodies and antibodies labeled with a radioisotope. A principal advantage of the method is that tumor responses can be obtained in a radiometric dose range that does not require hematopoietic stem cell replacement as an adjunct therapy.
Claims25
A method for immunotherapy of B-cell lymphoma, which comprises:
- (i) administering to a patient an imaging effective amount of an antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof, trace labelled with a first radiolabel, which binds to CD20 antigen present on the surface of cells of said B-cell lymphoma;
- (ii) imaging the distribution of said labelled antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof of step (i), within the body of the patient;
- (iii) administering to the patient an amount of the antibody or a Fab, Fab' or F(ab').sub.2 portion thereof of step (i) in unlabelled form, which binds to CD20 antigen present on the surface of cells of said B-cell lymphoma, said amount effective for blocking non-tumor binding sites for an antibody, or Fab, Fab' or F(ab').sub.2 portion thereof effective for treating B-cell lymphoma, within the body of the patient;
- and
- (iv) administering to the patient a radioimmunotherapeutically effective amount for treating B-cell lymphoma of said antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof of step (i), this is labelled with said first radiolabel or with a different radiolabel wherein the amount of radioactivity is less than the amount that provides irradiation at a dose which causes myelosuppression severe enough to require the reintroduction of hematopoietic stem cell into the patient in order for the to recover hematopoietic function after administration of said antibody or Fab, Fab' or F(ab').sub.2 portion thereof which is administered in said radioimmunotherapeutically effective amount.
2 more elements
A method for immunotherapy of a neoplasm of B cell lineage, which comprises:
- (i) administering to a patient an imaging effective amount of an antibody, or a Fab, Fab' or F(ab).sub.2, portion thereof, which binds to CD20 antigen present on the surface of cells of B lineage that is trace-labelled with a first radiolabel;
- (ii) imaging the distribution of said labelled antibody, or Fab, Fab' or F(ab').sub.2 portion thereof of step (i), within the body of the patient;
- (iii) administering to the patient an amount of the antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof of step (i) in unlabelled form, said amount being effective for blocking non-specific binding sites for an antibody effective for treating said neoplasm of B-cell lineage within the body of the patient;
- and
- (iv) administering to the patient a radioimmunotherapeutically effective amount for treating said neoplasm of B-cell lineage of said antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof of step (i), which binds to CD20 antigen present on the surface of said cells of B lineage, that is labelled with said first radiolabel or with a different radiolabel wherein the amount of radioactivity is less than the amount that provides irradiation at a dose which causes myelosuppression severe enough to require the reintroduction of hematopoietic stem cells into the patient in order for the patient to recover hematopoietic function after administration of said antibody, or Fab, Fab' or F(ab').sub.2 portion thereof which is administered in said radioimmunotherapeutically effective amount.
2 more elements
A method for immunotherapy of B-cell lymphoma, which comprises:
- (i) administering to a patient an imaging effective amount of an antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof, which binds to CD20 antigen present on the surface of cells of said B-cell lymphoma that is trace labelled with a radiolabel;
- (ii) imaging the distribution of said labelled antibody, or Fab, Fab' or F(ab').sub.2 portion thereof of step (i), within the body of the patient;
- (iii) administering to the patient an amount of the antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof of step (i) in unlabelled form, which binds to CD20 antigen present on the surface of cells of said B-cell lymphoma, said amount being effective for blocking non-tumor binding sites for an antibody effective for treating B-cell lymphoma within the body of the patient;
- and
- (iv) administering to the patient a radioimmunotherapeutically effective amount for treating B-cell lymphoma of said labelled antibody, or a Fab, Fab' or F(ab).sub.2 portion thereof of step (i), which binds to CD20 antigen present on the surface of cells of said B-cell lymphoma, wherein the amount of radioactivity is less than the amount that provides irradiation at a dose which causes myelosuppression severe enough to require the reintroduction of hematopoietic stem cells into the patient in order for the patient to recover hematopoietic function after administration of the radioimmunotherapeutically effective amount of said antibody, or Fab, Fab' or F(ab').sub.2 portion thereof which is administered in said radioimmunotherapeutically effective amount.
2 more elements
A method for immunotherapy of B-cell lymphoma, which comprises:
- (i) administering to a patient an effective amount of unlabeled antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof, which binds to CD20 antigen present on the surface of cells of said B-cell lymphoma, said amount effective for blocking non-tumor binding sites for said antibody in the body of said patient;
- (ii) administering an imaging effective amount of the antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof of step (i), which binds to CD20 antigen present on the surface of cells of said B-cell lymphoma, that is trace-labelled with a first radiolabel;
- (iii) imaging the distribution of said labelled antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof of step (ii), within the body of the patient;
- (iv) administering to the patient an amount of the unlabelled antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof, which binds to CD20 antigen present on the surface of cells of said B-cell lymphoma, said amount effective for blocking non-tumor binding sites for an antibody effective for treating B-cell lymphoma, or Fab, Fab' or F(ab').sub.2 portion thereof, within the body of the patient;
- and
- (v) administering to the patient a radioimmunotherapeutically effective amount for treating B-cell lymphoma of said antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof, of step (ii) which binds to CD20 antigen present on the surface of cells of said B-cell lymphoma, that is labelled with said first radiolabel or with a different radiolabel wherein the amount of radioactivity is less than the amount that provides irradiation at a dose which causes myelosuppression severe enough to require the reintroduction of hematopoietic stem cells into the patient in order for the patient to recover hematopoietic function after administration of said antibody or Fab, Fab' or F(ab').sub.2 portion thereof which is administered in said radioimmunotherapeutically effective amount.
3 more elements
A method for immunotherapy of B-cell lymphoma, which comprises:
- (i) administering to a patient a first amount of an unlabeled antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof, which binds to CD20 antigen present on the surface of cells of said B-cell lymphoma, said first amount effective for blocking non-tumor binding sites for said antibody in the body of said patient;
- (ii) administering to a patient an imaging effective amount of said antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof of step (i), which is trace-labeled with a first radiolabel;
- (iii) imaging the distribution of said labelled antibody, or Fab, Fab' or F(ab').sub.2 portion thereof of step (ii), within the body of the patient;
- (iv) administering to the patient a second amount of the unlabelled antibody, or a Fab, Fab' or F(ab').sub.2 portion thereof, as was used in step (i), said second amount effective for blocking non-tumor antibody binding sites within the body of the patient;
- and
- (v) administering to the patient a radioimmunotherapeutically effective amount for treating B-cell lymphoma of said antibody, or a Fab, Fab' or F(ab).sub.2 portion thereof of step (ii), which binds to CD20 antigen present on the surface of cells of said B-cell lymphoma, that is labelled with said first radiolabel or with a different radiolabel wherein the amount of radioactivity is less than the amount that provides irradiation at a dose which causes myelosuppression severe enough to require the reintroduction of hematopoietic stem cells into the patient in order for the patient to recover hematopoietic function after administration of said antibody, or Fab, Fab' or F(ab').sub.2 portion thereof which is administered in said radioimmunotherapeutically effective amount.
3 more elements
Dependencies are inferred from the claim text.