Fusion partner cells and uses thereof
View Patent ↗The present invention provides in one aspect novel fusion partner cells that ectopically express one or more genes that alter the phenotype of a hybrid cell made from a fusion of the fusion partner cell and a fusion cell, hybrid cell lines produced using the fusion partner cells. The invention in another aspect provides antibodies produced by certain hybrid cell lines, and compositions containing one or a combination of such antibodies or antigen-binding fragments thereof. The invention also provides in another aspect methods of using the antibodies or antigen-binding fragments thereof for diagnosis and treatment of diseases characterized by the antigens specifically bound by the antibodies.
1. A mouse B-lineage fusion partner cell comprising at least two ectopically expressed exogenous nucleic acid molecules, wherein
(a) each of the ectopically expressed nucleic acid molecules encodes a polypeptide that when expressed in a hybrid cell formed by the fusion of the fusion partner cell and a human B-lineage fusion cell, alters the phenotype of the hybrid cell;
(b) one of the at least two encoded polypeptides is IL-6 or IL-11, and one of the encoded polypeptides is hTERT; and
(c) the fusion partner cell is characterized in that fusion of the fusion partner cell with the human B-lineage fusion cell results in a hybrid cell that displays enhanced stability of antibody expression upon cloning of the hybrid cell, relative to the stability of antibody expression that would be observed if the fusion partner cell ectopically expressed IL-6 or hTERT but not both.
2. The mouse B-lineage fusion partner cell of claim 1 , wherein the B-lineage fusion partner cell is a myeloma or lymphoblastoid fusion partner cell.
3. A human B-lineage fusion partner cell comprising at least two ectopically expressed exogenous nucleic acid molecules, wherein
(a) each of the ectopically expressed nucleic acid molecules encodes a polypeptide that when expressed in a hybrid cell formed by the fusion of the fusion partner cell and a fusion cell, alters the phenotype of the hybrid cell, and
(b) one of the at least two encoded polypeptides is IL-6 or IL-11, and one of the encoded polypeptides is hTERT.
4. The human B-lineage fusion partner cell of claim 3 , wherein the fusion cell is a human B-lineage cell.
5. The human B-lineage fusion partner cell of claim 3 , wherein the fusion partner cell is a myeloma cell.
6. The human B-lineage fusion partner cell of claim 3 , wherein the at least two ectopically expressed nucleic acid molecules are expressed from one or more exogenously introduced expression cassettes.
7. The human B-lineage fusion partner cell of claim 6 , wherein the cassettes are included in viral vectors.
8. The human B-lineage fusion partner cell of claim 6 , wherein the cassettes are included in plasmid vectors.
9. The human B-lineage fusion partner cell of claim 7 , wherein the vectors are not integrated in one or more chromosomes.
10. The human B-lineage fusion partner cell of claim 6 , wherein the cassettes are integrated in one or more chromosomes.
11. The human B-lineage fusion partner cell of claim 6 , wherein there is more than one cassette, and wherein each cassette comprises at least one constitutive promoter operably linked to a nucleic acid molecule.
12. The human B-lineage fusion partner cell of claim 3 , wherein the B-lineage fusion partner cell is a myeloma or lymphoblastoid fusion partner cell.
13. A mammalian B-lineage fusion partner cell comprising at least two ectopically expressed exogenous nucleic acid molecules, wherein
(a) each of the ectopically expressed nucleic acid molecules encodes a polypeptide that when expressed in a hybrid cell formed by the fusion of the fusion partner cell and a fusion cell, alters the phenotype of the hybrid cell;
(b) one of the at least two encoded polypeptides is IL-6 or IL-11, and one of the encoded polypeptides is hTERT;
(c) the at least two ectopically expressed nucleic acid molecules are expressed from one or more exogenously introduced expression cassettes; and
(d) there is more than one cassette, and each cassette comprises at least one regulatable promoter operably linked to a nucleic acid molecule.
14. The mammalian B-lineage fusion partner cell of claim 13 , wherein the B-lineage fusion partner cell is a myeloma or lymphoblastoid fusion partner cell.
15. A mouse B-linage fusion partner cell comprising a soluble or membrane bound growth factor selected from the group consisting of IL-6 and IL-11 and at least one ectopically expressed exogenous nucleic acid molecule that encodes at least one polypeptide that when expressed in a hybrid cell formed by the fusion of the fusion partner cell and a human B-lineage fusion cell, alters the phenotype of the hybrid cell, wherein
(a) at least one encoded polypeptide is hTERT; and
(b) the fusion partner cell is characterized in that fusion of the fusion partner cell with the human B-lineage fusion cell results in a hybrid cell that displays enhanced stability of antibody expression upon cloning of the hybrid cell, relative to the stability of antibody expression that would be observed if the fusion partner cell did not ectopically express hTERT.
16. The mouse B-lineage fusion partner cell of claim 15 , wherein the B-lineage fusion partner cell is a myeloma or lymphoblastoid fusion partner cell.
17. A mammalian B-lineage fusion partner cell comprising a soluble or membrane bound growth factor selected from the group consisting of IL-6 and IL-11 and at least one ectopically expressed exogenous nucleic acid molecule that encodes at least one polypeptide that when expressed in a hybrid cell formed by the fusion of the fusion partner cell and a human B-lineage fusion cell, alters the phenotype of the hybrid cell, wherein
(a) at least one encoded polypeptide is hTERT; and
(b) the fusion partner cell is characterized in that fusion of the fusion partner cell with the human B-lineage fusion cell results in a hybrid cell that displays enhanced stability of antibody expression upon cloning of the hybrid cell, relative to the stability of antibody expression that would be observed if the fusion partner cell did not ectopically express hTERT.
18. The mammalian B-lineage fusion partner cell of claim 17 , wherein the B-lineage fusion partner cell is a myeloma or lymphoblastoid fusion partner cell.
19. A mouse B-lineage fusion partner cell comprising a soluble or membrane bound growth factor selected from the group consisting of IL-6 and IL-11 and at least one ectopically expressed exogenous nucleic acid molecule that encodes at least one polypeptide that when expressed in a hybrid cell formed by the fusion of the fusion partner cell and a primary human B-lineage fusion cell, alters the phenotype of the hybrid cell, wherein;
(a) at least one encoded polypeptide is hTERT; and
(b) the fusion partner cell is characterized in that fusion of the fusion partner cell with the primary human B-lineage fusion cell results in a hybrid cell that displays enhanced stability of antibody expression upon cloning of the hybrid cell, relative to the stability of antibody expression that would be observed if the fusion partner cell did not ectopically express hTERT.
20. The mouse B-lineage fusion partner cell of claim 19 , wherein the B-lineage fusion partner cell is a myeloma or lymphoblastoid fusion partner cell.
21. A mouse B-lineage fusion partner cell comprising at least two ectopically expressed exogenous nucleic acid molecules, wherein
(a) each of the ectopically expressed nucleic acid molecules encodes a polypeptide that when expressed in a hybrid cell formed by the fusion of the fusion partner cell and a primary human B-lineage fusion cell, alters the phenotype of the hybrid cell;
(b) one of the at least two encoded polypeptides is IL-6 or IL-11, and one of the encoded polypeptides is hTERT; and
(c) the fusion partner cell is characterized in that fusion of the fusion partner cell with the primary human B-lineage fusion cell results in a hybrid cell that displays enhanced stability of antibody expression upon cloning of the hybrid cell, relative to the stability of antibody expression that would be observed if the fusion partner cell ectopically expressed IL-6 or hTERT but not both.
22. The mouse B-lineage fusion partner cell of claim 21 , wherein the B-lineage fusion partner cell is a myeloma or lymphoblastoid fusion partner cell.
23. A mammalian B-lineage fusion partner cell comprising at least two ectopically expressed exogenous nucleic acid molecules, wherein
(a) each of the ectopically expressed nucleic acid molecules encodes a polypeptide that when expressed in a hybrid cell formed by the fusion of the fusion partner cell and a human B-lineage fusion cell, alters the phenotype of the hybrid cell;
(b) one of the at least two encoded polypeptides is IL-6 or IL-11, and one of the encoded polypeptides is hTERT; and
(c) the fusion partner cell is characterized in that fusion of the fusion partner cell with the human B-lineage fusion cell results in a hybrid cell that displays enhanced stability of antibody expression upon cloning of the hybrid cell; relative to the stability of antibody expression that would be observed if the fusion partner cell ectopically expressed IL-6 or hTERT but not both.
24. The mammalian B-lineage fusion partner cell of claim 23 , wherein the B-lineage fusion partner cell is a myeloma or lymphoblastoid fusion partner cell.