Glycan-modified anti-CD4 antibodies for HIV prevention and therapy
Disclosed herein are glycan-modified anti-CD4 monoclonal antibodies with N-linked glycans attached to the variable region. Expression vectors and cell lines useful for the production of such antibodies, and use of such antibodies for HIV prevention and therapy are also disclosed.
1. A glycan-modified antibody comprising N-linked glycans attached to a variable region of said antibody, wherein said antibody comprises a heavy chain comprising three CDRs contained in SEQ ID NO: 2 and a light chain comprising three CDRs contained in SEQ ID NO:3, and comprises an engineered N-linked glycosylation site at an amino acid position in the sequence of SEQ ID NO:3 selected from the group consisting of amino acid 54 of SEQ ID NO:3 (30EGln), amino acid 77 of SEQ ID NO:3 (52Ser), amino acid 78 of SEQ ID NO:3 (53Thr), amino acid 79 of SEQ ID NO:3 (54Arg), amino acid 85 of SEQ ID NO:3 (60Asp), amino acid 90 of SEQ ID NO:3 (65Ser), amino acid 92 of SEQ ID NO:3 (67Ser), and amino acid 101 of SEQ ID NO:3 (76Ser).
2. The antibody of claim 1 , wherein the one or more N-linked glycans are attached to the variable region of the light chain of said antibody.
3. The antibody of claim 1 , wherein the engineered N-linked glycosylation site is located at an amino acid position of the light chain selected from the group consisting of 30EGln, 52Ser, 53Thr, 54Arg, 65Ser, and 67Ser.
4. The antibody of claim 3 , wherein the engineered N-linked glycosylation site is located at 52Ser.
5. The antibody of claim 4 , wherein said light chain comprises an amino acid sequence of the light chain as set forth in SEQ ID NO: 4.
6. A glycan-modified antibody comprising N-linked glycans attached to a variable region of said antibody, wherein said antibody comprises a light chain and a heavy chain, wherein said light chain comprises an amino acid sequence of the light chain set forth in SEQ ID NO:4 and wherein said heavy chain comprises an amino acid sequence of the heavy chain as set forth in SEQ ID NO: 5.
7. The antibody of claim 1 , wherein the N-linked glycans comprise at least 7 carbohydrate units.
8. The antibody of claim 7 , wherein the N-linked glycans comprise 10-11 carbohydrate units.
9. A pharmaceutical composition comprising the antibody of claim 1 and at least one pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising the antibody of claim 6 and at least one pharmaceutically acceptable carrier.