Saturday, August 20, 2016

Selective Tregs elimination within tumor using CD25 antibody coupled to near-infrared photoimmunotherapy

Regulatory T cells (Tregs) inhibit immune responses. When considering autoimmune diseases or allergies, this function of Tregs has beneficial effect on host. The same function, however, could be "hijacked" by tumors to evade immune destruction. So far, selective depletion of tumor-associated Tregs has not been achieved in clinical settings.

New paper in Science Translational Medicine suggested novel approach to eliminate tumor-associated Tregs: application of anti-CD25 F(ab)2 fragments coupled to photo-active silica-phthalocyanine dye (IR700)  and exposed to near-infrared photo-immunotherapy (NIR-PIT)

First, in vitro experiments showed that when CD25+ cells are exposed to anti-CD25 F(ab)2-IR700 and subjected to NIR-PIT, they undergo cell death.

Since tumors accumulate high frequency of Tregs, the authors conducted NIR-PIT experiments in vivo. When tumor-challenged mice were exposed to anti-CD25 F(ab)2-IR700 and subjected to NIR-PIT, the authors observed temporal delay in tumor growth and improved survival

Of note, tumors located at the distant sites away from direct exposure of NIR-PIT also display growth delay after anti-CD25 F(ab)2-IR700/NIR-PIT application, indicating system-wide after-effect of local elimination of Tregs by NIR-PIT.

Finally, the authors found that anti-tumor effect of anti-CD25 F(ab)2-IR700/NIR-PIT application was mediated by IFN-gamma derived from CD8 T and NK cells.

In summary, the authors claim that this less invasive procedure could selectively eliminate CD25+ Tregs (but not effector T cells) in tumors  and improve survival of tumor-challenged host.

David Usharauli

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