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Mogamulizumab mechanism of action and measuring the response to treatment

3rd Nov 2021

Interview and article by Christine Clark, PhD, FRPharmS.

Mogamulizumab is a humanised monoclonal antibody that selectively binds to C-C chemokine receptor 4 (CCR4). CCR4 is involved in trafficking of lymphocytes to skin and is expressed on the surface of tumour cells in certain T-cell malignancies.

When mogamulizumab is used to treat cutaneous T-cell lymphoma (CTCL) the response is usually monitored by assessment of all four affected anatomical compartments – skin, lymph nodes, viscera and blood.

Mogamulizumab is an antibody that selectively binds to CCR41 and elicits anti-tumour activity by antibody-dependent cellular cytotoxicity (ADCC).2 CCR4 in association with its ligands – the chemokines thymus- and activation-regulated chemokine (TARC, CCL17) and macrophage-derived chemokine (MDC, CCL22)3 – is involved in the trafficking of T-cells to the skin as part of normal immunosurveillance.4,5 In CTCL it is also involved in the trafficking of skin-homing neoplastic T-cells, leading to local immune responses and skin manifestations.5

CCR4 is also expressed on T-regulatory (Treg) cells and mogamulizumab-induced depletion of T-reg cells6 may also contribute to the overall anti-tumour effects.

Assessing response
Professor Pablo Ortiz-Romero (Dermatology Department, Hospital 12 de Octubre Medical School, Madrid Spain) describes how the response to treatment is monitored:

The response to treatment is measured using disease-specific international consensus guidelines7 by assessment of all four affected anatomical compartments – skin, lymph nodes, viscera and blood.
The skin response is measured using the mSWAT (modified severity weighted assessment tool) that takes account of the percentage of body surface area affected and the type and severity of lesions. This “translates into numbers … what the patient has on the skin” on a scale from 0 to 400, says Professor Ortiz. Peripheral blood is assessed using flow cytometry. Lymph node and visceral involvement is assessed by CT scan or PET-CT scan.

References

  1. Potiligeo (mogamulizumab) Summary of Product Characteristics
  2. Kim YH et al Lancet 2018;19:1192-1204
  3. Yoshie O & Matsushima K. CCR4 and its ligands: from bench to bedside. Int Immunol. 2015 Jan;27(1):11-20. doi: 10.1093/intimm/dxu079.
  4. Ferenczi K et al J Invest Dermatol 2002;119:1405-1410
  5. Girardi M et al. N Engl J Med2004;350:1978-1988
  6. Ni X et al. Clin Cancer Res. 2015;21:274-85.  doi: 10.1158/1078-0432.CCR-14-0830
  7. Olsen EA et al. J Clin Oncol 2011;29:2598-2607

 

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