Mechanism of action and discussion

Unlike conventional immunosuppressive drugs, photopheresis may retain a balance between tolerance and necessary physiological defences against pathogens.¹²

Photopheresis does not suppress immunity against either new or recall challenges.^13,15

It is considered to have an immunomodulatory rather than an immunosuppressive effect.^13,15

Although the mechanism of action of THERAKOS™ Photopheresis is not clearly understood, two theories have been proposed to explain the beneficial effects of therapy:^44,6,8,10

Tolerogenic theory
This theory proposes that photopheresis efficacy is determined by the induction of antigen-specific immune tolerance. Tolerance may be achieved due to:

• Alterations in antigen-presenting cell (APC) populations
• Alterations in cytokine secretion
• Induction of regulatory T-cells (Tregs), which regulate the immune system

Vaccination theory
This theory proposes that photopheresis efficacy is based on anti-idiotypic T-cell receptor (TCR) vaccination, whereby the cell separation process of photopheresis induces monocytes to differentiate into immature activated dendritic cells. These dendritic cells then:¹

• Phagocytose apoptotic cells
• Present tumour antigens on their cell surfaces
• Elicit the equivalent of a vaccine response, with proliferation and increased
  function of anti-tumour effector cells