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Msg  11443 of 19431  at  6/13/2019 12:54:39 AM  by


The following message was updated on 6/13/2019 12:59:08 AM.

 In response to msg 11431 by  Coronado1
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Re: Dr. Rosenberg's Group: Neoantigens in patients with gastrointestinal cancers, pub. 6/4/19

king coronado, were you able to download the entire pdf of this paper? 
can i get a copy?
dogged asked me what i thought about today, kinda think it is what we expected. 
i also replied to eatsmelt and i do think that there may already be multiple patients who have already been considered for the trial based on their haplotype and the mutation, and i am now thinking it would be the Kras mutation they go after initially in the trial, but i expect dr Rosenberg will go with the patients he feels have the best chance to respond, and try to include as many as possible that his group can handle. 
this trial really is his victory lap in a way. he was the one pulling for SB from way back. in fact i sometimes wonder if the reason dr Cooper got MDAnderson to buy up the rights to SB was because he and dr Rosenberg had thought about this from way back then, already over 10-11 years ago.
 i expect we will continue to rally in the stock price, with the shorts taking their profits now before they lose all of their gains. remember that many if not most of them are short from over $12-14 so they would be trying to get out with as much profit now as possible imo.
no way to know when some form of news will spook them into a mad dash to cover like we see in intrexon now but i would expect they will get some help from anal fearstein making more derogatory comments to give them more time to cover.
but eventually this will become national news and it could provoke a big rally at any time imo, when they get some of the first responses to the therapy.  but that could be 4-6 months out too. just glad to see it finally rolling and that patients will finally get a chance to survive this horrible malignancy. surprised it is not already making news.
again about the library of off the shelf solutions:
the T cell has an immune activation when it sees the specific MHC-peptide complex that it has been created for, actually by random creation by the V(D)J recombinase system which creates the TCR of the T cell.
the MHC is the HLA of the human, and there is a huge range of possible HLA expressed throughout the human population. 
the mutation is for an individual amino acid in the sequence of 8-9 amino acids that make up the epitope and it can be anywhere in that 8-9 AA sequence, but the TCR can recognize it as non self, when it is bound up in that patient's specific MHC, or HLA as we call it.
so the library they are talking about is the AA sequence of that specific mutation which when combined with the same MHC-I, (HLA) will be recognized by the neoantigen specific TCR and that allows them to immediately create from their known coding sequence of the alpha and beta chains of the TCR that will give that patient with the same HLA as the one that the library sequence is specific for, a rapid turnaround from the initial tumor excision and enhancement steps, to the coding sequence of the DNA, oligonucleotides, that make the plasmid for the TCR that is then transduced into the naive T cell from the peripheral blood so the patient can receive the enhanced Teff population in a short period of time. maybe about 2-3 weeks instead of about 6-8 weeks if the neoantigen has to be identified by using the tandem minigene technique to create the AA sequence that the patient's 'reactive' T cells will respond to, in the ELISpot assay, which then gives them the clue to know what the specific T cell is that responds to the neoantigen, from the TIL. then they can do the single cell seqPCR to find the RNA sequence of that T cell that is reactive to the epitope discovered in the tandem minigene process. and each of these discovered sequences will be added to the library along with the patients specific HLA or haplotype. 
so every patient now will become another little dot in the library and over time this will optimize the identification process to make the time to treatment shorter and shorter, and help to keep the costs down. all of this stuff takes expensive lab work and expensive reagents too. these FACS machines have revolutionized this stuff, and they are not cheap either i bet, along with the skills needed to do this stuff. 

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Msg # Subject Author Recs Date Posted
11445 Re: Dr. Rosenberg's Group: Neoantigens in patients with gastrointestinal cancers, pub. 6/4/19 Biotech2050 1 6/13/2019 1:01:44 AM

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