The lysate is all they need! Neoantigens end up getting targeted naturally provided they go after the appropriate mutations that have binding capabilities.
I tried to explain it yesterday to you and probably did so poorly, simplified. GBM is divided into 4 subtypes of cancer. Each one of them has their own specific mutations. Mesenchymal has the most. They need to target each one specifically. But instead of treating them with known targets, like MAA antigen (though they will likely still add that one) they are going to run sequencing to determine the exact epitope with that has HLA-1 binding (killer T). And they will do that with each specific mutation. And then they will also include HLA-2 binding antigens (helper T).
Eventually, they then will be able to run test on the individual patients tumor to create the exact matching epitopes and antigen the patients needs for their tumor. That is why UCLA is keeping all the tumor. And if the tumor has suppressive factors, coming from macrophages they will be able to combine with CI.
Example, as I only have BC to use:
Breast cancer is generally divided into three subtypes: estrogen receptor/progesterone receptor-positive, HER-2/neu receptor-positive, and triple negative breast cancers.
Now, think of GBM Mesenchymal as BC HER-2/neu receptor-positive cancer. Pretend when you read this study that they are talking about one specific mutation in Mesenchymal (even though the example is all HER-2/neu)
HER-2/neu antigen is a 23-mer, p362–384, QEFAGCKKIFGSLAFLPESFDGD.
If NW Bio would use the above 23-mer, if it's present in a patients subtype tumor lysate. But, NW Bio still needs the lysate broken down into peptides as DC cells can only process peptides. It potentially has hundreds antigens in the vaccine. So for instance with HER-2/neu it could end up coming with the some of the following peptides: p368–376, KKIFGSLAF; p372–380, GSLAFLPES; p364–373, FAGCKKIFGS; and p373–382, SLAFLPESFD. They would use the appropriate HLA-1 and HLA-2 after sequencing. So they would pick p373–382, SLAFLPESFD.
Now read the article and see if you can understanding the sequencing work that is done to find the appropriate epitope.
J Immunol. 2013 Jan 1;190(1):479-88. doi: 10.4049/jimmunol.1201264. Epub 2012 Nov 23.
Enzymatic discovery of a HER-2/neu epitope that generates cross-reactive T cells.
Abstract Patients with HER-2/neu-expressing breast cancer remain at risk for relapse following standard therapy. Vaccines targeting HER-2/neu to prevent relapse are in various phases of clinical testing. Many vaccines incorporate the HER-2/neu HLA-A2-binding peptide p369-377 (KIFGSLAFL), because it has been shown that CTLs specific for this epitope can directly kill HER-2/neu-overexpressing breast cancer cells. Thus, understanding how tumors process this epitope may be important for identifying those patients who would benefit from immunization. Proteasome preparations were used to determine if p369-377 was processed from larger HER-2/neu-derived fragments. HPLC, mass spectrometry, cytotoxicity assays, IFN-? ELISPOT, and human breast cancer cell lines were used to assess the proteolytic fragments. Processing of p369-377 was not detected by purified 20S proteasome and immunoproteasome, indicating that tumor cells may not be capable of processing this Ag from the HER-2/neu protein and presenting it in the context of HLA class I. Instead, we show that other extracellular domain HER-2/neu peptide sequences are consistently processed by the proteasomes. One of these sequences, p373-382 (SLAFLPESFD), bound HLA-A2 stronger than did p369-377. CTLs specific for p373-382 recognized both p373-382 and p369-377 complexed with HLA-A2. CTLs specific for p373-382 also killed human breast cancer cell lines at higher levels than did CTLs specific for p369-377. Conversely, CTLs specific for p369-377 recognized p373-382. Peptide p373-382 is a candidate epitope for breast cancer vaccines, as it is processed by proteasomes and binds HLA-A2.
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