Humanized monoclonal antibodies and methods of use

摘要

The present invention comprises a humanized monoclonal antibody that binds to the chemokine receptor CCR4. This antibody is derived from Mab 1567 and recognizes the same epitope. Binding of the invented antibody to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer. Moreover, the antibody is used in combination with vaccines to suppress the activity of regulatory T cells.

主权项

1. A method of selectively killing a tumor cell comprising contacting said cell with a composition comprising a humanized monoclonal CC-chemokine receptor 4 (CCR4) antibody or fragment thereof, wherein said antibody has the following characteristics:
a. binds to CCR4 positive (CCR4+) cells but not CCR4 negative (CCR4−) cells; b. decreases binding of a ligand or agonist to the CCR4 receptor; and wherein said antibody comprises i. a heavy chain variable region encoded by the nucleic acid sequence comprising:
CAGGTGCAGCTGGTGCAGAGCGGAGCCGAGGTGAAGAAGCCTG GAGCTTCCGTCAAGGTGTCCTGCAAGGCCAGCGGCTACACCTTC GCCAGCTACTACATGCACTGGATGCGGCAGGCACCTGGACAGG GCCTCGAATGGATCGGCTGGATCAACCCCGGCAACGTGAACAC CAAGTACAACGAGAAGTTCAAGGGCAGGGCCACCCTGACCGTG GACACCAGCACCAACACCGCCTACATGGAACTGAGCAGCCTGC GGAGCGAGGACACCGCCGTGTACTACTGCGCCAGAAGCACCTA CTACCGGCCCCTGGACTACTGGGGCCAGGGCACCCTGGTGACC GTGAGCAGC (SEQ ID NO:1); or ii. a heavy chain variable region comprising the amino acid sequence:
QVQLVQSGAEVKKPGASVKVSCKASGYTFASYYMHWMRQAPG QGLEWIGWINPGNVNTKYNEKFKGRATLTVDTSTNTAYMELS SL RSEDTAVYYCARS TYYRPLDYWGQGTLVTVSS (SEQ ID NO:2); and iii. a light chain variable region encoded by the nucleic acid sequence comprising:
GACATCGTGATGACCCAGAGCCCCGACAGCCTGGCCGTGAGCC TGGGCGAGCGGGCCACCATCAACTGCAAGAGCAGCCAGAGCA TCCTGTACAGCAGCAACCAGAAGAACTACCTGGCCTGGTATCA GCAGAAGCCCGGCCAGAGCCCCAAGCTGCTGATCTACTGGGCC AGCACCCGGGAGAGCGGCGTGCCCGACCGGTTTAGCGGCAGC GGCTCCGGCACCGACTTCACCCTGACCATCAGCAGCCTGCAGG CCGAGGACGTGGCCGTGTACTACTGCCACCAGTACCTGAGCAG CTACACCTTCGGCCAGGGCACAAAGCTGGAAATCAAG (SEQID NO:3); or iv. a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERATINCKSSQSILYSSNQKNYLAWYQQKPG QSPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC HQYLSSYTFGQGTKLEIK (SEQ ID NO:4).