Stabilized radiolabeled anti-CD45 immunoglobulin compositions
Compositions and methods are described for stabilizing a radio-iodinated monoclonal IgG antibody for up to 17 days against radiolytic decomposition. The stabilized radiolabeled murine antibody binding the CD45 antigen expressed on various forms of lymphomas is useful as a radiotherapeutic and diagnostic agent in the treatment of human malignancies of hematopoietic origin, including lymphomas.
1 . A method for treating a subject afflicted with a hematologic malignancy, the method comprising:
administering by intravenous administration to the subject a therapeutically effective amount of an aqueous pharmaceutical composition comprising:
a monoclonal antibody against CD45, wherein the antibody is radiolabeled with 131 I, and comprises
a heavy chain having heavy chain complementarity determining regions with amino acids sequences as set forth in SEQ ID NOS: 6-8, and an aspartic acid at position 14, and
a light chain having light chain complementarity determining regions with amino acids sequences as set forth in SEQ ID NOS: 3-5; and
a pharmaceutically acceptable carrier comprising 0.5% to 5.0% (w/v) of ascorbic acid and 0.5% to 4.0% (w/v) of PVP,
wherein the aqueous pharmaceutical composition is administered either alone or in conjunction with another form of treatment; and
wherein the hematologic malignancy is selected from the group consisting of acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma.
2 . The method of claim 1 , wherein the hematologic malignancy is acute myeloid leukemia, and the subject is relapsed or refractory, and at least 55 years old.
3 . The method of claim 1 , wherein the other form of treatment comprises a bone marrow transplant.
4 . A method for ablating bone marrow cells in a subject afflicted with acute myeloid leukemia prior to the subject's receiving a bone marrow transplant, the method comprising:
administering by intravenous administration to the subject a therapeutically effective amount of an aqueous pharmaceutical composition comprising:
a monoclonal antibody against CD45, wherein the antibody is radiolabeled with 131 I, and comprises
a heavy chain having heavy chain complementarity determining regions with amino acids sequences as set forth in SEQ ID NOS: 6-8, and an aspartic acid at position 14, and
a light chain having light chain complementarity determining regions with amino acids sequences as set forth in SEQ ID NOS: 3-5; and
a pharmaceutically acceptable carrier comprising 0.5% to 5.0% (w/v) of ascorbic acid and 0.5% to 4.0% (w/v) of PVP.
5 . A method for treating a subject afflicted with a hematologic malignancy, the method comprising:
administering by intravenous administration to the subject a therapeutically effective amount of an aqueous pharmaceutical composition comprising:
a monoclonal antibody against CD45, wherein the antibody is radiolabeled with 131 I, and comprises a light chain having light chain complementarity determining regions with amino acids sequences as set forth in SEQ ID NOS: 3-5, and
a pharmaceutically acceptable carrier comprising 0.5% to 5.0% (w/v) of ascorbic acid and 0.5% to 4.0% (w/v) of PVP,
wherein the aqueous pharmaceutical composition is administered either alone or in conjunction with another form of treatment; and
wherein the hematologic malignancy is selected from the group consisting of acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma.
6 . The method of claim 5 , wherein the hematologic malignancy is acute myeloid leukemia, and the subject is relapsed or refractory, and at least 55 years old.
7 . The method of claim 5 , wherein the other form of treatment comprises a bone marrow transplant.
8 . The method of claim 5 , wherein the heavy chain of the radiolabeled antibody comprises an aspartic acid at position 14.
9 . The method of claim 1 , wherein the effective amount is a therapeutic dose.
10 . The method of claim 9 , wherein the therapeutic dose is 100 to 1,500 mCi of 131 I radioactivity.
11 . The method of claim 4 , wherein the effective amount is a therapeutic dose.
12 . The method of claim 11 , wherein the therapeutic dose is 100 to 1,500 mCi of 131 I radioactivity.
13 . The method of claim 5 , wherein the effective amount is a therapeutic dose.
14 . The method of claim 13 , wherein the therapeutic dose is 100 to 1,500 mCi of 131 I radioactivity.