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Reference 17 at the bottom of the article posted by Bermuda is worth following.
It caught my eye because it is about CD4+ TCells becoming cytotoxic.
There is a link to this particular article
https://doi.org/10.1084/jem.20091918
Note that James Allison is one of the authors of this article
Here's a snippet from the article
"Surprisingly, CD4+ T cells developed cytotoxic activity, and tumor rejection was dependent on class II–restricted recognition of tumors by tumor-reactive CD4+ T cells. Furthermore, blockade of the coinhibitory receptor CTL-associated antigen 4 (CTLA-4) on the transferred CD4+ T cells resulted in greater expansion of effector T cells, diminished accumulation of tumor-reactive regulatory T cells, and superior antitumor activity capable of inducing regression of spontaneous mouse melanoma."
It sounds like James and his mates were using "Ipy" to add to the potency of the "surprising" CD4+ cytotoxic TCells.
but the key in bermuda's link
is """abnormal phosphorylation is a hallmark of malignancy"""
Glycolysis
Glycolysis is an essential process of glucose degrading into two molecules of pyruvate, through various steps, with the help of different enzymes. It occurs in ten steps and proves that phosphorylation is a much required and necessary step to attain the end products. Phosphorylation initiates the reaction in step 1 of the preparatory step[11] (first half of glycolysis), and initiates step 6 of payoff phase (second phase of glycolysis).[12]
Glucose, by nature, is a small molecule with the ability to diffuse in and out of the cell. By phosphorylating glucose (adding a negatively charged phosphate group), glucose is converted to glucose-6-phosphate and trapped within the cell as the cell membrane is negatively charged. This reaction occurs due to the enzyme hexokinase, an enzyme that helps phosphorylate many six-membered ring structures. Glucose-6-phosphate cannot travel through the cell membrane and is therefore, coerced to stay inside the cell. Phosphorylation takes place in step 3, where fructose-6-phosphate is converted to fructose-1,6-bisphosphate. This reaction is catalyzed by phosphofructokinase.
While phosphorylation is performed by ATPs during preparatory steps, phosphorylation during payoff phase is maintained by inorganic phosphate. Each molecule of glyceraldehyde-3-phosphate is phosphorylated to form 1,3-bisphosphoglycerate. This reaction is catalyzed by GAPDH (glyceraldehyde-3-phosphate dehydrogenase). The cascade effect of phosphorylation eventually causes instability and allows enzymes to open the carbon bonds in glucose.
Phosphorylation functions as an extremely vital component of glycolysis, for it helps in transport, control and efficiency.[13
Its a key part of life ... Ray
Phosphorylated proteins appears to be a well researched subject.
https://en.wikipedia.org/wiki/Phosphorylation
Scroll down to the section entitled "Protein phosphorylation".
Over 240,000 articles on the subject, most of which are about protein phosphorylation.
I notice our old friends arginine and lysine get a mention.
Also Mass Spectrometry gets a mention which is the method used to detects PTMs being used in one of Lindy's sponsored projects at Durham and Liverpool universities.
Bermuda bottom of the first page and 2nd ...
https://www.scancell.co.uk/Data/Sites/1/media/publications/papers/biofeb19web_choudhury.pdf
We all know that the prinicple behind Moditope is targeting proteins that have undergone post translational modifications(PTMs). In the case of Modi1, the PTM is citrullination and one of the primary targets is the protein Vimentin.
Some interesting research from Asahikawa Medical University, Japan was published yesterday - 'Phosphorylated vimentin as an immunotherapeutic target against metastatic colorectal cancer'
Phosphorylation is another very common post translational modification and the researchers from Asahikawa have found that phosphorylated vimentin is upregulated in colorectal cancer and 'targeting phosphorylated vimentin is a feasible approach for the treatment of metastatic tumors while sparing non-tumor cells'. Their conclusion - 'These results suggest that immunotherapy targeting phosphorylated vimentin could be promising for metastatic CRC patients.'
Link is below but unfortunately the whole paper is behind a paywall so you can only access the abstract but worth noting that Lindy Durrant's 2016 research on citrullinated vimentin is cited. Really good to see interest building in this field, it can only help Scancell's cause.
https://link.springer.com/article/10.1007%2Fs00262-020-02524-9