Mogamulizumab-kpkc

Brand Name: Poteligeo

Mogamulizumab-kpkc is used to treat mycosis fungoides and Sézary syndrome.1

How Does Mogamulizumab-kpkc Work?

TARC binds to CCR4 and promotes T cell homing towards the skin.

CCR4 is a receptor protein found on the surface of some T cells, a type of immune cell. CCR4 binds to a signaling protein called TARC2, which is commonly produced in the skin.3 This allows CCR4-expressing T cells to home in to the skin.

Non-T cell surface with a few CCR4, followed by T cell and lymphoma cell surface with numerous CCR4.

In general, non-T cells express little to no CCR4 on their surface. On the other hand, skin-homing T cells and skin-associated T cell lymphoma cells express large amounts of CCR4 on their surface, which provides a target to specifically recognize and kill these cancer cells.4

Mogamulizumab-kpkc bound to CD20.

Mogamulizumab-kpkc is an antibody drug that can recognize and bind to CCR4.5

Antibody receptor on natural killer cells recognize mogamulizumab-kpkc and releases toxins to kills cancer cells.

(1) Natural killer (NK) cells, a type of immune cells, express antibody receptors on their surface that can recognize antibodies. When these receptors bind to antibodies like mogamulizumab-kpkc, NK cells are activated. (2) Active NK cells release toxins that (3) punctures and kills nearby cells.6 Since mogamulizumab-kpkc specifically recognizes CCR4, cells expressing the highest amounts of CCR4, i.e. the lymphoma cells, are targeted for killing by natural killer cells, while most other cells are spared.7

References

1. POTELIGEO. U.S. Food and Drug Administration (2022).

2. Imai, T. et al. The T Cell-directed CC Chemokine TARC Is a Highly Specific Biological Ligand for CC Chemokine Receptor 4. Journal of Biological Chemistry 272, 15036-15042 (1997).

3. Campbell, J. J. et al. The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature 400, 776-780 (1999).

4. Ferenczi, K., Fuhlbrigge, R. C., Kupper, T. S., Pinkus, J. L. & Pinkus, G. S. Increased CCR4 Expression in Cutaneous T Cell Lymphoma. Journal of Investigative Dermatology 119, 1405-1410 (2002).

5. Niwa, R. et al. Defucosylated Chimeric Anti-CC Chemokine Receptor 4 IgG1 with Enhanced Antibody-Dependent Cellular Cytotoxicity Shows Potent Therapeutic Activity to T-Cell Leukemia and Lymphoma. Cancer Research 64, 2127-2133 (2004).

6. Wang, W., Erbe, A. K., Hank, J. A., Morris, Z. S. & Sondel, P. M. NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy. Frontiers in Immunology 6, 368 (2015).

7. Varchetta, S. et al. Elements Related to Heterogeneity of Antibody-Dependent Cell Cytotoxicity in Patients Under Trastuzumab Therapy for Primary Operable Breast Cancer Overexpressing Her2. Cancer Research 67, 11991-11999 (2007).