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Skeletons Keys
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This is a coronavirus
If you have ever picked a lock it is T-cell therapy that has a lot in common with lock picking, a painstaking business that often ends in frustration. Every virus, like every lock, presents a unique challenge. We need to reverse engineer some cancer research that was just released this morning. Just imagine a thing such as an anticancer [anti viral] T cell that worked as though it carried a skeleton key? This T cell is equipped with a T-cell receptor (TCR) that bypasses obstructions and engages a shared mechanism, that is, a mechanism common to the locks, presented by different kinds of cancers and viruses.
This is a GMO Skeleton Key in T cell mucous cells
A skeleton key–like TCR hasn’t been found on ordinary T cells. However, one has been discovered on the keychain of another kind of T cell, the mucosal-associated invariant T (MAIT) cell. In humans, MAIT cells are found in the blood, liver, lungs, and mucosa, defending against microbial activity and infection. Unlike ordinary T cells, which fumble over molecular locks involving the human leukocyte antigen (HLA) system, MAIT cells have a TCR that works with another cell surface display system, the monomorphic MHC class I-related protein, MR1.
The new discovery, which comes from scientists based at Cardiff University, raises the possibility of developing pan-cancer/pan-viral and pan-population cancer/viral immunotherapies.
The usual target of T-cell therapies is an HLA system, which varies widely between individuals. The MR1 system, however, does not vary in the human population—meaning it is a hugely attractive new target for immunotherapies. Immunotherapies are under the auspices of Precision Medicine, therefore requiring your blood to treat your condition genetically, offering you a genetically modified solution for your unique body.
Targeting via MR1-restricted T cells is an exciting new frontier—it raises the prospect of a ‘one size fits all’ treatment, a single type of T cell that could destroy many different types of cancers and [viruses] across the population.”
Sewell is the senior author of an article (“Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer-targeting via the monomorphic MHC class I-related protein MR1”) that appeared in Nature Immunology. According to this article, the MR1-targeting TCR from MAIT cells “recognized and killed most human cancer types … while remaining inert to noncancerous cells.” This would hold true for viral types although this study was not examining viruses.
Graphic depicting how a T-cell receptor enables pan-cancer cell recognition via the invariant MR1 molecule. [Andrew Sewell, Cardiff University]
T cells equipped with the new TCR were shown, in the lab, to kill lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney, and cervical cancer cells, while ignoring healthy cells. To test the therapeutic potential of these cells in vivo, the researchers injected T cells able to recognize MR1 into mice bearing human cancer and with a human immune system.
This showed “encouraging” cancer-clearing results, which the researchers said were comparable to those obtained using a conventional chimeric antigen receptor (CAR) T-cell therapy in a similar animal model. The Cardiff group also showed that T cells of melanoma patients modified to express this new TCR could destroy not only the patient’s own cancer cells but also other patients’ cancer cells in the laboratory, regardless of the patient’s HLA type.
In currently approved T-cell therapies, immune cells are removed, modified, and returned to the patient’s blood to seek and destroy cancer cells. The most widely used version of this therapy, the CAR T-cell therapy, is personalized to each patient [that is Precision Medicine].
The team performed experiments to determine the precise molecular mechanism by which the new TCR distinguishes between healthy cells and cancer.
In other words, the researchers believe the TCR may work by sensing changes in cellular metabolism that cause different metabolic intermediates to be presented at the cancer cell surface by MR1.
“There are plenty of hurdles to overcome,” Sewell noted.
Mutagenesis Due to Cosmic Rays
As scientists seek to deploy this genetically modified skeleton key we need to remember that we are being bombarded by invisible cosmic particles that are breaking our DNA creating mutagenesis in our bodies. Some of the biomarkers we have reviewed include complex clustered DNA damage, persistent DNA repair foci, reactive oxygen species [of which T cells are a part of], chromosome aberrations and inflammation. Other biomarkers discussed, often assayed for at longer points post-exposure, include mutations, chromosome aberrations, reactive oxygen species, and telomere length changes.
It appears that the biological Pandora’s Box has been opened at the perfect environmental timing as cosmic rays surge to historic records creating biological vulnerabilities in our bodies.
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Celeste has worked as a contractor for Homeland Security and FEMA. Her training and activations include the infamous day of 911, flood and earthquake operations, mass casualty exercises, and numerous other operations. Celeste is FEMA certified and has completed the Professional Development Emergency Management Series.
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Celeste grew up in military & governmental home with her father working for the Naval Warfare Center, and later as Assistant Director for Public Lands and Natural Resources, in both Washington State and California.
Celeste also has training and expertise in small agricultural lobbying, Integrative/Functional Medicine, asymmetrical and symmetrical warfare, and Organic Farming.
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