Ugur Sahin Research Papers27 Jan 2019 11:44
As a consequence, there is an ample need for a technology enabling the systematic recovery of sets of functional TCRs against defined antigens from individual repertoires as well as swift definition of their specificity.
The pool of antigens potentially suitable as immunotherapeutic targets for TCR-engineered T cells has grown considerably. However, for the vast majority of these antigens, neither TCRs nor T-cell clones have been defined as yet.
its interest that he goes on about NY-ESO-1
For further proof of concept, we resorted to NY-ESO-1, one among the immunologically best-characterized members of the cancer/germline antigen family. NY-ESO-1 is known to frequently elicit spontaneous CD4+ and CD8+ T-cell responses in patients with cancer, the specificities of which have been mapped over the last few years. Sixteen NY-ESO-1–specific TCRs were isolated from 3 seropositive patients with non–small cell lung cancer (NSCLC). These were directed against 11 different HLA class-I and -II restricted epitopes, again known and novel ones, clustering in known immunogenic regions of the NY-ESO-1 protein.
Then you look at SCIB2
To broaden the application of this vaccination strategy, 16 NY-ESO-1 epitopes, covering over 80% of HLA phenotypes, were incorporated into the IB (SCIB2). They produced higher frequency and avidity T cell responses than peptide vaccination.
You see even BioNtechs work .... Agrees with Scancells ...
now look at this ............
In summary, we identified 398 TCRs representing 189 different clonotypes. Among these, 56 TCRs were shown to be antigen specific corresponding to approximately one third of the uniquely identified TCRs. Notably, the majority of specificities have not been described earlier, although 2 of the antigens have been extensively studied as T-cell antigens for decades now. Moreover, the majority of TCRs were shown to recognize HLA class-II restricted epitopes, whereas the currently available and clinically explored TCRs are all HLA class-I restricted epitopes. The CD4+ T cells are of particular interest, as coadministration of CD4+ T cells to TCR-engineered adoptively administered T cells has been shown to enhance tumor infiltration of CD8+ T cells and to prevent their exhaustion.
"""" the majority of TCRs were shown to recognize HLA class-II restricted epitopes """"
on CD4 can see that class II epitopes ...
so they are struggling to find CD8's targets ...........
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938367/
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