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TCRT-PGEN Fundamental & Technical Discussion Board
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Dmun ... moving to the crux for confirmation.So the Rapid Cloning paper of February, 2020 (REF: Inv Vllg Z-P board, message #16097)... which I have thought is a keystone in TCR-T success ... in simple terms -- begins with if you can find each distinct neoantigen in a patient's tumor, then you can kill the cancer. IMO, said again, "find each unique neoantigen" is the keystone to cure. The patient's Sleeping Beauty (SB) plasmid DNA is combined with various alpha/beta receptor DNA designs (a/b TCRs happens to cover about 90% of all T cell receptor designs in humans) and this modified SB interrogation process is a rapid (two-day) step. Those varying neoantigens designs that get held by the varying designed arms "express" or fluoresce, and by their reaction, the arms are matching up and identifying the exact DNA design of the several, distinct neoantigen that are present in the tumor. From this key step, the Tcell and TCRs can be then be synthetically produced for electroporation onto the patient's SB plasmid, the plasmids are grown in large numbers infused to become the therapeutic solution. This research, it is noteworthy imo, is wholly MDA-authored (Cooper also listed). SB is MDA's patent (Cooper as sole patent author), I would add becomes the "cheap," rapid and practical agent for not only "the find," but also the solution. If I have this simplified explanation about right, my question becomes -- in simple terms, by what means does Ziopharm or the NCI use to make sure the interrogation is thorough? While P53 or KRAS families of multiple designs can be routinely employed, does this paper also explain how to find the anomalous neoantigens that are specific only to each patient? (Ref: Drs. Drew and Steve -- virtually all solid cancer have a neoantigen design that is unique to that patient). My own assumption is that the SB plasmid for interrogation can incorporate several designs, suggested by the clinician's experience with the type of cancer, and/or, artificial intelligence which may be used when even "slight" levels of single-cell fluorescence appear. Thanks in advance. Please be patient and write as if explaining to a child. As Paris Hilton once said, "I'm ... like ... not that smart." My remaining question is foundational to ownership and ties to the "IF-Then" opening. Perhaps the "thoroughness" explanation is buried in the complexity of this very same paper or perhaps another paper. Again, thanks. |
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