New off-the-shelf cancer vaccine reduces metastasis in animal experiments

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2 pointsmarc__11 comment

"We developed a conceptually new cancer vaccine that targets a tumour immune escape mechanism. The vaccine targets the MICA and MICB (MICA/B) stress proteins that are upregulated in response to DNA damage in many types of human cancers but are expressed at low or undetectable levels by healthy cells.
Engagement of the activating NKG2D receptor by membrane-bound MICA/B trig-gers the cytotoxicity programme in natural killer (NK) cells and co-stimulatory signalling in CD8+ Tcells7–9. However, many human tumours evade this important immune recognition pathway by proteolytic shedding of MICA/B from the cell surface.
Shedding substantially reduces the surface density on tumour cells of these immunostimulatory ligands for the NKG2D receptor. Shed MICA/B proteins have also been reported to induce NKG2D recep-tor internalization and inhibit NK cell function12,14–16. Patients with melanoma responding to an autologous cell-based cancer vaccine (GVAX) plus anti-CTLA-4 were found to develop anti-MICA antibod-ies, and the presence of these antibodies correlated with reduced serum levels of shed MICA and augmented CD8+ Tcell and NK cell responses.
Design of the MICA and MICB α3 domain vaccine:

Our vaccine targeted the highly conserved α3 domain in MICA/B, the site of proteolytic shedding, and was designed to induce tumour immunity by Tcells and NK cells (Fig.1a)19. We intentionally omitted the α1–α2 domains to avoid induction of antibodies that could block NKG2D receptor binding20."

https://www.nature.com/articles/s41586-022-04772-4.epdf

https://www.technologynetworks.com/cancer-research/news/off-...

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