Pharmaceutical compositions comprising humanized anti-CCR4 IgG4 antibody
The present disclosure provides methods of modulating regulatory T-cell activity and function.
1. A pharmaceutical composition comprising a humanized anti-CCR4 antibody in an amount effective to increase the ratio of effector T-cells to regulatory T-cells in or associated with a tumor present in a human subject to whom the pharmaceutical composition is administered one or more times,
wherein the regulatory T-cells comprise CD4 + CD25 highCD127dim/− Tregs and the effector T-cells comprise CD4 + CD25 − Teffs,
wherein the humanized anti-CCR4 antibody has a heavy chain with three CDRs comprising the amino acid sequences GYTFASAW (SEQ ID NO: 9), INPGNVNT (SEQ ID NO: 11), and STYYRPLDY (SEQ ID NO: 13) respectively and a light chain with three CDRs comprising the amino acid sequences QSILYSSNQKNY (SEQ ID NO: 10), WASTRE (SEQ ID NO: 12), and HQYMSSYT (SEQ ID NO: 14) respectively, and
wherein the humanized anti-CCR4 antibody has an IgG 4 heavy chain constant region.
2. The pharmaceutical composition of claim 1 , wherein the tumor is a solid tumor.
3. The pharmaceutical composition of claim 1 , wherein the humanized anti-CCR4 IgG4 antibody is non-immunodepleting.
4. The pharmaceutical composition of claim 1 , wherein the constant region comprises a S228P mutation.