Killer Cells Lay Mines to Blast Cancerous, Infected Cells

May 20, 2020 | Biotechnology

Reading time: 2-3 minutes

Genetic Engineering and Biotechnology News (GEN) published an interesting article covering Biotech:

Cytotoxic T lymphocytes (CTLs) are versatile killers. When they detect a target—a cell infected by a virus or deranged by cancer—they can release soluble proteins that punch holes in a targeted cell’s membrane, exposing the targeted cell’s innards to toxic enzymes that cause it to self-destruct. But that’s not all, report scientists based at the University of Oxford. According to these scientists, CTLs may release supramolecular attack particles (SMAPs), which may attach to (and destroy) a target cell straightaway, or linger in the intracellular environment autonomously. The upshot is that SMAPS—glycoprotein shells packed with “explosive” cytotoxic proteins—may act as hand grenades or land mines.

That CTLs may act as minelayers is a new observation, one that became possible though a collaboration between the University of Oxford scientists and researchers at the Harwell Science and Innovation Campus who operate the B24 beam line at the Diamond Light Source. Using cryo-soft-X-ray tomography, the collaborators probed the core-shell physical nature of SMAPs and determined that SMAPs, upon release from CTLs, remain stable and retain cytotoxic potential. That is, SMAPs may lie in wait, ready to detonate. But what is the trigger?

SMAP structure and the SMAP triggering mechanism were addressed in a paper (“Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells”) that appeared May 7 in the journal Science. The paper not only described shell-core SMAP granules, it also presented a working model for SMAP function. SMAP granules, the paper explained, may act as autonomous killing entities with innate targeting through thrombospondin-1, a shell component.

“Mass spectrometry, immunochemical analysis, and CRISPR editing identified a C-terminal fragment of thrombospondin-1 as an une... You can read the whole article in the GEN Blog.

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