Vaccine clinical trials for new diagnosis of glioblastoma

It is shown that APVAC1-induced T-cell function and PTP-013 can be presented via HLA peptidesOf the 13 patients, 9 (69.2%) showed an answer to CD4-T cells of 1 to 2 unmutated HLA-II peptide antigens in APVAC1, with a total immunogenicity of 50% of these peptidesCurrently, immunocheckpoint inhibitors have good anti-tumor effects on many types of tumors, but the treatment of glioblastoma (GBM) is not idealBecause it relies on the tumor's high frequency mutation load and its response to the new antigen epitopeIn glioblastoma, immune cell immersion is limited, and glioblastoma contains only 30-50 nonsympliallantsUsing tumor unmutated antigens and new epitopes, it may be possible to provide effective immunotherapy for glioblastomawith with low frequency mutation loadsThe Phase I (GAPVAC-101) trial of the Glioma Personalized Vaccine Alliance (GAPVAC) found that highly personalized vaccination and integration of two types of tumor antigen therapy in newly diagnosed glioblastoma patients can achieve extremely strong immunogenicityNorbert Hilf of The Biot, Tubingen, Germany, published the results online in December 2018in melanoma studies, new tumor antigens selected through tumor vaccinehave strong immunogenicity and effectiveness in clinical applicationsHowever, only a small number of mutations produce new antigens that Are T-cells can identify and present by human leukocyte antigens (HLA)For tumors with fewer mutations, non-antigen-specific immunotherapy, such as immunocheckpoint inhibitors, may not be fully effectiveIn glioblastoma, T-cells have good clinical treatment when they react effectively to non-mutation and overexpression antigens, and can be an important part of targeted new antigen and anti-tumor therapythe authors used XPRESIDENT technology to detect non-mutated, HLA-presented new antigens in 30 glioblastoma samplesIn the end, 33 polypeptide supted revenue libraries combined with HLA-A-02 and 26 combined HLA-A-24:02Each peptide tumor antigen and each tumor transcription group in the preparation library were tested by mass spectrometry and microarray analysis to understand the response in each case of GAPVAC-101 patientsBased on the results of the analysis, the authors designed an active individualized vaccine (APVAC1) containing 7 of the best HLA-Ipeptides, two combination of HLA-II polypeptides and 1 viral marker polypeptide then, to see if APVAC1 can induce an immune response An exosome polypolymer analysis showed that 12 of the 13 patients had CD8-T cells induced by the HLA-I peptide vaccine for APVAC1, producing more than 1 reaction (92.3%; median 3 reactions); After vaccination, APVAC1-specific T-cells are converted into memory-type T cells The 16 patients who were vaccinated at pbMC (PTP T cells) and THE APVAC1-induced PTP-013 reactive CD8-T cells can be highly bound to kill the K562-A2 target cells that express peptides These T cells can also crack the glioblastoma cell line L2, and endogenous expression PTP-013 (PTPRZ1) It is shown that APVAC1-induced T-cell function and PTP-013 can be presented via HLA peptides Of the 13 patients, 9 (69.2%) showed an answer to CD4-T cells of 1 to 2 unmutated HLA-II peptide antigens in APVAC1, with a total immunogenicity of 50% of these peptides the recurrence and decline of the tumor through imaging examination when APVAC1 treatment is applied In the months following chemotherapy and assisted TMZ treatment, imaging tests often revealed changes in tumor lesions 26.8 months after the diagnosis of GBM, patients with recurrence of the tumor were given re-removal of the tumor, and the test results confirmed that the CD8-T cells around the tumor were highly immersed with FOXP3-Treg cells Tumors containing CD4-T cells can react directly to THE HLA-II peptide PTP-010 of APVAC1.