Article Text

Download PDFPDF

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
  1. Santosh Kesari1,
  2. Daniela Bota2,
  3. David Piccioni3,
  4. Christopher Duma4,
  5. Renato LaRocca5,
  6. Xiao-Tang Kong2,
  7. Frank Hsu2,
  8. Jose Carrillo1,
  9. Mehrdad Abedi6,
  10. Robert Aiken7,
  11. Thomas Taylor2,
  12. Aleksandra Poole8,
  13. Candace Hsieh8,
  14. Gabriel Nistor8 and
  15. Robert Dillman8
  1. 1John Wayne Cancer Institute, Santa Monica, CA, USA
  2. 2University of California Irvine, Orange, CA, USA
  3. 3University of California San Diego, San Diego, CA, USA
  4. 4Hoag NeuroSciences Institute, Newport Beach, CA, USA
  5. 5Norton Cancer Institute, Louisville, KY, USA
  6. 6University of California Davis, Sacramento, CA, USA
  7. 7Rutgers Cancer Center, New Brunswick, NJ, USA
  8. 8AIVITA Biomedical, Inc., Irvine, CA, USA


Background 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 with AV-GBM-1, a personal vaccine consisting of autologous dendritic cells (DC) pulsed with autologous tumor antigens (ATA) may improve survival. One objective of a multi-center phase II clinical trial was to determine changes in blood proteomics before and after injections of AV-GBM-1.

Methods AV-GBM-1 consists of autologous DC incubated with ATA from a lysate of irradiated autologous GBM cells that had been placed in culture and incubated in serum-free medium with factors that favor the survival and proliferation of stem cells and early progenitor cells. After recovery from RT/TMZ, GBM patients were injected subcutaneously with AV-GBM-1 admixed in granulocyte-macrophage colony-stimulating factor (GM-CSF) at weeks 1, 2, 3, 8, 12, 16, 20, and 24. Blood samples obtained at baseline (week-0), just prior to the third injection (week-2) and just prior to the fourth injection (week-8), were cryopreserved and subsequently analyzed for 448 proteomic markers using quantitative, multiplex enzyme-linked immunosorbent assays (Raybiotech, Inc., Norcross, GA.). In this preliminary analysis the averages of paired samples for each time point were determined and compared using the student T-Test with a focus on differences of p<0.01.

Results Patients were enrolled from five sites in California, and one each in Kentucky and New Jersey. 57 patients were treated during November 2018 to October 2020. Paired samples from all three time points were available for 49 patients. After two weekly injections there were increases in thymus-and activation-regulated chemokine (TARC, CCL17), the chemotactic protein chemerin, lipocalin-2, (expressed by macrophages and epithelium in response to inflammation) and angiopoietin-1 (suppressor of vascular inflammation), and decreases in thrombospondin-5 (possibly involved in synaptogenesis in brain repair), angiotensinogen (a precursor of all angiotensin peptides), and beta-fibroblast growth factor (important in tissue repair). The increase in TARC (p<0.0000001) was attributed to GM-CSF; TARC had declined almost to baseline levels by week-8. The other six markers had p values between 0.0011 and 0.0087. The only marker that was still changed at week-8 was thrombospondin-5 (p=0.023).

Conclusions If there were humoral changes in proteins associated with Th1 and Th2 responses, these were no longer present after two weekly vaccinations. More sophisticated analyses of this data set, such as principal component analysis, may be needed to understand the effects of AV-GBM-1.

Clinicaltrials gov NCT03400917

Ethics Approval This study was approved by the Western IRB, approval number 20182582; all participants gave written informed consent before taking part

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.