Methods of mediating cytokine expression with anti ccr4 antibodies
AssigneeDana-Farber Cancer Institute, Inc.
InventorWayne A. MARASCO
Life of this patent
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Abstract
The present disclosure provides methods of modulating regulatory T-cell activity and function.
Claims34
A method of depleting regulatory T-cells (Tregs) in a subject comprising administering to a subject in need thereof a humanized anti-CCR4 antibody having:
- 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);
- 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.
A method of inhibiting migration of regulatory T-cells (Tregs) to a cytokine secreting tumor in a subject comprising administering to a subject having a cytokine secreting tumor humanized anti-CCR4 antibody having:
- 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.
A method of any one of the preceding claims, wherein effector T-cells are not substantially depleted.
A method of any one of the preceding claims, wherein the ratio of effector T cells to regulatory T-cells is modulated in the tumor or subject.
The method of any one of the preceding claims, wherein effector T-cell number is increased or not substantially reduced.
The method of any one of the preceding claims, wherein cytokine release from an effector T-cell population is modulated.
The method of any one of the preceding claims, wherein an effector polypeptide release from an effector T-cell population is modulated.
The method of any one of the preceding claims, wherein the regulatory T-cell is a follicular regulatory T-cells.
A method of inhibiting tumor cell growth in a subject comprising administering to a subject in need thereof a humanized anti-CCR4 antibody having 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.
A method of vaccinating for an antigen comprising administering to a subject the antigen and an anti-CCR4 antibody.
A method of anyone of the preceding claims-wherein the humanized anti-CCR4 antibody is a first member of a bispecific antibody.
A method of inhibiting IL-2 binding to CCR4+ Tregs comprising contacting said Tregs with a humanized anti-CCR4 antibody having:
- 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.
A method of inducing CD25 cleavage comprising contacting a Treg with a humanized anti-CCR4 antibody having:
- 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.
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Dependencies are inferred from the claim text.