Light chain immunoglobulin fusion proteins and methods of use thereof
Provided are recombinant antibodies comprising one or more peptides fused to the C-terminus of the light chain constant region. Recombinant immunocytokines comprising a cytokine fused to the C-terminus of the light chain constant region are described and shown to be surprisingly active.
1. A fusion protein comprising a cytokine which is:
(i) IL2,
(ii) human IL2,
(iii) human IL2, wherein the length of the N-terminal region of the cytokine fusion is shortened by 1 to 10 amino acids of the N-terminal region of SEQ ID NO: 13, or
(iv) IL2 having a mutation at one or more positions corresponding in human IL2 of SEQ ID NO: 13 to D20, F42, R38, N88, or Q126;
wherein the fusion protein retains cytokine activity, and wherein the fusion protein comprises one antibody comprising two heterodimers, each heterodimer comprising
a) a full-length antibody heavy chain, and
b) a full-length antibody light chain fused at its C-terminus, without a linker peptide, to the cytokine,
wherein each heterodimer comprises only a single cytokine,
and
wherein the antibody specifically binds to an antigen expressed on the extracellular surface of a tumor cell.
2. The fusion protein of claim 1 , wherein the full-length antibody heavy chain is an IgG heavy chain.
3. The fusion protein of claim 2 , wherein the IgG heavy chain is an IgG 1 heavy chain.
4. The fusion protein of claim 2 , wherein the IgG heavy chain is an IgG 2 or IgG 3 or IgG 4 heavy chain.
5. The fusion protein of claim 1 , wherein the light chain constant region is a Cκ constant region.
6. The fusion protein of claim 1 , wherein the light chain constant region is a Cλ constant region.
7. A composition comprising the fusion protein of claim 1 .
8. A pharmaceutical composition comprising (i) a therapeutically effective amount of the fusion protein of claim 1 , and (ii) a pharmaceutically acceptable carrier.