Breaking News: the Human Body’s Serial Killer Caught on Tape
A team led by Professor Griffiths at the University of Cambridge has captured in a stunning video the behaviour of cytotoxic T cells encountering cancer cells through high-resolution 3D time-lapse multi-colour imaging, obtained using avant-garde microscopy techniques.
If you were walking up and down the isles of your favourite high tech store browsing the latest ultra flat, high definition TV, undecided which one to go for, you will probably do a double take at the one broadcasting strange green and red amorphous blobs in a pitch black field, moving around rapidly by pushing out their leading edge, as if they were investigating their environment as they travel.
Intrigued by what you see, you may initially convince yourself that you are looking at the trailer of the latest sci-fi movie and then be once again struck by the realisation that instead you are watching at a reality show in which the main players are tiny motile cells, called cytotoxic T cells, that have been captured on camera while encountering and executing a cancer cell. Cytotoxic T cells patrol our bodies in search of abnormalities like virally infected or cancer cells, which they are able to recognize with remarkable precision and to efficiently destroy. They are the undisputed super stars of our immune system that we have now learnt to isolate from cancer patients biopsies or bone marrow and expand or genetically modify ex vivo to render them even stronger in fighting cancer.
The surprisingly detailed video was taken using sophisticated microscopy techniques by a team of researcher led by Professor Griffiths founded by the Wellcome Trust, at the University of Cambridge. The video – which complements a study published last week on Immunity – helps unravelling the temporal order of events occurring when cytotoxic T cells come in contact with virally infected or transformed (cancer) cells.
Cytotoxic T cells can be seen rapidly extending membrane protrusions to explore the surface of the neighbouring cells, trying to engage in cell-cell contacts via surface receptors that help them understand whether they are dealing with an uninvited guest. These cell-cell communications have been proficiently exploited by immunotherapeutics such as Ipilimumab (Yervoy™), pembrolizumab (Keytruda®), and nivolumab (Opdivo), whose mechanisms of action were described in our previous blog posts.
Once T cells bind to cancer cells they release cytotoxins, which can be seen travelling down membrane protrusions on cellular railways called actin microtubules and then being discharged into the unwanted cell. This precise mechanism of delivery ensures that T cells specifically target unwanted bodies without causing collateral damage to the surrounding healthy cells. Once cytotoxins are injected into cancer cells, their fate is sealed and they can be seen blebbing away and dying while T cells moves on to the next target.
Given their impressive efficacy it is perhaps not surprising that T cells have been the focus of the latest efforts in anticancer drug discovery. Immunotherapeutic agents are in the pipeline of most pharmaceutical companies that are now experimenting new combinatorial approaches as well as inhibition of new regulatory checkpoints to ensure that T cells stay active in cancer patients. Immunotherapy has shown unprecedented results in terms of patients progression-free-survival and remission rates and dominates the clinical trial landscape for cancer types such melanoma, lung, or mesothelioma that had very limited treatment options until not too long ago.
At Crown Bioscience we are excited to see the immune system being the focus of such ground breaking scientific investigation at all levels, from basic research to translational studies. We support research in immunotherapy with a range of platforms, with either murine or human immunity. Our immunotherapy resources include syngenic (bioluminescent and metastatic) models, GEMM, MuPrime™ (the murine version of HuPrime® which is the world’s largest collection of well-characterized and validated Patient-Derived Xenograft models), HuMice™ (humanized mice produced through inoculating human hematopoietic cells into immunocompromised mice), and MiXeno™ (creating transient human immunity by mixing human peripheral blood mononucleated cells with xenograft models). We also support preclinical drug development through the use of our in vivo grade human and mouse isotype control antibodies.
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