targetsTarget

CCR4

CCR4 is a chemokine receptor on skin-homing and regulatory T cells, and on the malignant cells of cutaneous T-cell lymphoma and adult T-cell leukaemia; mogamulizumab removes those cells.

CCR4 binds CCL17/CCL22 and marks Th2 and regulatory T cells and most CTCL, Sézary and ATLL cells. Mogamulizumab (afucosylated anti-CCR4) depletes them by ADCC (MAVORIC). Because it also depletes Tregs, CCR4 blockade is being combined with checkpoint inhibitors in solid tumours (small molecules FLX475, mogamulizumab-nivolumab), so far with modest results. CCR4 gain-of-function mutations occur in ~25% of ATLL.

CCR4: what it is and how drugs act on it · animated generic schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · CCR4 is a chemokine receptor on skin-homing and regulatory T cells, and on the malignant cells of cutaneous T-cell lymphoma and adult T-cell leukaemia; mogamulizumab removes those cells.

1 · What it is
CCR4 is a chemokine receptor on skin-homing and regulatory T cells, and on the malignant cells of cutaneous T-cell lymphoma and adult T-cell leukaemia; mogamulizumab removes those cells.
2 · What goes wrong in cancer
GPCR expressed on Th2, Th17 and Treg cells and skin-homing T cells; chemotaxis to CCL17/CCL22 produced by dendritic cells and keratinocytes.
3 · How drugs use it
1 product aims at CCR4: antibodies. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.

Biology

GPCR expressed on Th2, Th17 and Treg cells and skin-homing T cells; chemotaxis to CCL17/CCL22 produced by dendritic cells and keratinocytes.

Where it is found

Mycosis fungoides / Sézary syndrome (>80%)
Adult T-cell leukaemia/lymphoma (~90%; 25% mutated)
Peripheral T-cell lymphoma (subset)
Tumour-infiltrating Tregs in solid tumours

Class

surface antigen · CCR4

Products

1top

Not mapped hereDefucosylated anti-CCR4 monoclonal antibody

Mogamulizumab · Poteligeo

Mogamulizumab is an antibody that clears cancerous T cells from the blood in mycosis fungoides and Sézary syndrome, the leukaemic form of skin lymphoma.