333 Changes in proteomic markers after injections of personal AV-GBM-1 dendritic cell/tumor initiating cell vaccines in a phase II trial in patients with newly diagnosed glioblastoma

• DOI: 10.1136/jitc-2021-sitc2021.333
• Publication Date: 2021-11-09T15:08:54Z
• Authors: Santosh Kesari; Daniela Bota; David Piccioni; Christopher Duma; Renato LaRocca; Xiao-Tang Kong; Frank Hsu; Jose Carrillo; Mehrdad Abedi; Robert Aiken; Thomas Taylor; Aleksandra Poole; Candace Hsieh; Gabriel Nistor; Robert Dillman
• Keywords: Temozolomide; Clinical endpoint

<h3>Background</h3> Despite standard aggressive therapy, including maximum safe surgical resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ, survival is still extremely poor for patients with newly diagnosed primary glioblastoma (GBM). Adding treatment AV-GBM-1, a personal vaccine consisting of autologous dendritic cells (DC) pulsed tumor antigens (ATA) may improve survival. One objective multi-center phase II clinical trial was to determine changes in blood proteomics before after injections AV-GBM-1. <h3>Methods</h3> AV-GBM-1 consists DC incubated ATA from lysate irradiated GBM that had been placed culture serum-free medium factors favor the proliferation stem early progenitor cells. After recovery RT/TMZ, were injected subcutaneously admixed granulocyte-macrophage colony-stimulating factor (GM-CSF) at weeks 1, 2, 3, 8, 12, 16, 20, 24. Blood samples obtained baseline (week-0), just prior third injection (week-2) fourth (week-8), cryopreserved subsequently analyzed 448 proteomic markers using quantitative, multiplex enzyme-linked immunosorbent assays (Raybiotech, Inc., Norcross, GA.). In this preliminary analysis averages paired each time point determined compared student T-Test focus on differences p&lt;0.01. <h3>Results</h3> Patients enrolled five sites California, one Kentucky New Jersey. 57 treated during November 2018 October 2020. Paired all three points available 49 patients. two weekly there increases thymus-and activation-regulated chemokine (TARC, CCL17), chemotactic protein chemerin, lipocalin-2, (expressed macrophages epithelium response inflammation) angiopoietin-1 (suppressor vascular inflammation), decreases thrombospondin-5 (possibly involved synaptogenesis brain repair), angiotensinogen (a precursor angiotensin peptides), beta-fibroblast growth (important tissue repair). The increase TARC (p&lt;0.0000001) attributed GM-CSF; declined almost levels week-8. other six p values between 0.0011 0.0087. only marker changed week-8 (p=0.023). <h3>Conclusions</h3> If humoral proteins associated Th1 Th2 responses, these no longer present vaccinations. More sophisticated analyses data set, such as principal component analysis, be needed understand effects <h3>Trial Registration</h3> <h3>Clinicaltrials</h3> gov NCT03400917 <h3>Ethics Approval</h3> This study approved Western IRB, approval number 20182582; participants gave written informed consent taking part