Monoclonal antibodies against CD30 lacking in fucosyl residues
View Patent ↗The invention pertains to anti-CD30 antibodies that lack fucosyl residues. The antibodies of the invention exhibit increased antibody-dependent cellular cytotoxicity (ADCC) activity, including the ability to lyse CD30-expressing cell lines that are not lysed by the fucosylated form of the antibodies. The invention also provides host cells that express the anti-CD30 antibodies that lack fucosyl residues, wherein the host cells are deficient for a fucosyl transferase. Methods of using the antibodies to inhibit the growth of CD30+ cells, such as tumor cells, are also provided.
1. An isolated full length IgG1 anti-CD30 antibody, which lacks fucose residues, wherein the antibody comprises a heavy chain variable region CDR1 comprising SEQ ID NO: 7, a heavy chain variable region CDR2 comprising SEQ ID NO: 10, a heavy chain variable region CDR3 comprising SEQ ID NO: 13, a light chain variable region CDR1 comprising SEQ ID NO: 16, a light chain variable region CDR2 comprising SEQ ID NO: 19, and a light chain variable region CDR3 comprising SEQ ID NO: 22.
2. The antibody of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 1 and the light chain variable region comprises the amino acid sequence of SEQ ID NO:4.
3. The antibody of claim 1 , which is a monoclonal antibody.
4. The antibody of claim 1 , which is a human, humanized or chimeric antibody.
5. The antibody of claim 1 , wherein the antibody is linked to a toxin.
6. A method of inhibiting growth of CD30 + cells comprising contacting said cells with the antibody of claim 1 under conditions sufficient to induce antibody-dependent cellular cytotoxicity (ADCC) of said cells.
7. The method of claim 6 , wherein said cells are tumor cells.
8. The method of claim 6 , wherein said anti-CD30 antibody is a human antibody.
9. A method of inhibiting growth of tumor cells expressing CD30 in a subject, comprising administering to the subject the antibody of claim 1 , in an amount effective to inhibit growth of tumor cells expressing CD30 in the subject.
10. The method of claim 9 , wherein said anti-CD30 antibody is a human antibody.
11. The method of claim 9 , wherein said tumor cells are Hodgkin's Disease (HD) tumor cells.
12. The method of claim 9 , wherein said tumor cells are anaplastic large-cell lymphoma (ALCL) tumor cells.
13. The method of claim 9 , wherein the tumor cells are from a disease selected from the group consisting of non-Hodgkin's lymphoma, Burkitt's lymphoma, cutaneous T-cell lymphomas, nodular small cleaved-cell lymphomas, lymphocytic lymphomas, peripheral T-cell lymphomas, Lennert's lymphomas, immunoblastic lymphomas, T-cell leukemia/lymphomas (ATLL), adult T-cell leukemia (T-ALL), entroblastic/centrocytic (cb/cc) follicular lymphomas cancers, diffuse large cell lymphomas of B lineage, angioimmunoblastic lymphadenopathy (AILD)-like T cell lymphoma, adult T-cell lymphoma (ATL), HIV associated body cavity based lymphomas, Embryonal Carcinomas, undifferentiated carcinomas of the rhino-pharynx (e.g., Schmincke's tumor), Castleman's disease, Kaposi's Sarcoma, CD30+ T-cell lymphomas and CD30+ B-cell lymphomas.