Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof
Cancer treatments use a therapy that: 1) interferes with the interaction between CD200 and its receptor to block immune suppression thereby promoting eradication of the cancer cells; and 2) directly kills the cancer cells either by complement-mediated or antibody-dependent cellular cytotoxicity or by targeting cells using a fusion molecule that includes a CD200-targeting portion. The therapy includes the administration of novel antibodies, functional fragments thereof or fusion molecules containing portions thereof.
1. A method of treating a human afflicted with a cancer comprising cancer cells expressing human CD200 protein, the method comprising:
administering to the human a therapeutic composition comprising an anti-CD200 antibody or antigen-binding fragment thereof, the antibody or antigen-binding fragment being present in an amount sufficient to promote production of one or more Th1 cytokines in the human to thereby treat the cancer, wherein the anti-CD200 antibody or antigen-binding fragment thereof binds to human CD200 protein expressed on the cancer cells and wherein the anti-CD200 antibody or antigen-binding fragment thereof inhibits the interaction between human CD200 and the human CD200 receptor,
wherein the anti-CD200 antibody or antigen-binding fragment thereof comprises:
(A): (i) a light chain polypeptide comprising: a light chain CDR3 having the sequence set forth in residues 91-99 of SEQ ID NO: 209; a light chain CDR2 having the sequence set forth in residues 52-58 of SEQ ID NO: 209; and a light chain CDR1 having the sequence set forth in residues 26-36 of SEQ ID NO: 209; and (ii) a heavy chain polypeptide comprising: a heavy chain CDR3 having the sequence set forth in SEQ ID NO: 195; a heavy chain CDR2 having the sequence set forth in SEQ ID NO: 174; and a heavy chain CDR1 having the sequence set forth in SEQ ID NO: 149; or
(B): (i) a light chain polypeptide having an amino acid sequence comprising the amino acid sequence depicted in SEQ ID NO: 209; and (ii) a heavy chain polypeptide having an amino acid sequence comprising the amino acid sequence depicted in SEQ ID NO: 203.
2. A method of killing cancer cells expressing human CD200 protein, the method comprising:
administering to a human afflicted with a cancer comprising cancer cells expressing human CD200 protein a therapeutic composition comprising an anti-CD200 antibody, the antibody in an amount sufficient to kill cancer cells expressing human CD200 protein in the human by antibody-dependent cell-mediated cytotoxicity (ADCC), wherein the anti-CD200 antibody comprises a human heavy chain Fc region that effectuates ADCC, and wherein the anti-CD200 antibody binds to human CD200 protein expressed by the cancer cell,
wherein the anti-CD200 antibody comprises:
(A): (i) a light chain polypeptide comprising: a light chain CDR3 having the sequence set forth in residues 91-99 of SEQ ID NO: 209; a light chain CDR2 having the sequence set forth in residues 52-58 of SEQ ID NO: 209; and a light chain CDR1 having the sequence set forth in residues 26-36 of SEQ ID NO: 209; and (ii) a heavy chain polypeptide comprising: a heavy chain CDR3 having the sequence set forth in SEQ ID NO: 195; a heavy chain CDR2 having the sequence set forth in SEQ ID NO: 174; and a heavy chain CDR1 having the sequence set forth in SEQ ID NO: 149; or
(B): (i) a light chain polypeptide having an amino acid sequence comprising the amino acid sequence depicted in SEQ ID NO: 209; and (ii) a heavy chain polypeptide having an amino acid sequence comprising the amino acid sequence depicted in SEQ ID NO: 203.
3. A method of treating a human afflicted with a cancer comprising cancer cells expressing CD200 protein, the method comprising:
administering to the human a therapeutic composition comprising an anti-CD200 antibody, the antibody in an amount sufficient to treat the cancer by (i) promoting production of one or more Th1 cytokines in the human and (ii) killing cancer cells expressing human CD200 protein in the human by complement dependent cytotoxicity (CDC) or antibody-dependent cell-mediated cytotoxicity (ADCC), wherein the anti-CD200 antibody comprises a human heavy chain Fc region that effectuates CDC or ADCC, and wherein the anti-CD200 antibody binds to human CD200 protein expressed by the cancer cell,
wherein the anti-CD200 antibody comprises:
(A): (i) a light chain polypeptide comprising: a light chain CDR3 having the sequence set forth in residues 91-99 of SEQ ID NO: 209; a light chain CDR2 having the sequence set forth in residues 52-58 of SEQ ID NO: 209; and a light chain CDR1 having the sequence set forth in residues 26-36 of SEQ ID NO: 209; and (ii) a heavy chain polypeptide comprising: a heavy chain CDR3 having the sequence set forth in SEQ ID NO: 195; a heavy chain CDR2 having the sequence set forth in SEQ ID NO: 174; and a heavy chain CDR1 having the sequence set forth in SEQ ID NO: 149; or
(B): (i) a light chain polypeptide having an amino acid sequence comprising the amino acid sequence depicted in SEQ ID NO: 209; and (ii) a heavy chain polypeptide having an amino acid sequence comprising the amino acid sequence depicted in SEQ ID NO: 203.