Course Hero Logo

41940-PB2-4604-R2.pdf - Editorial Commentary Vaccines...

Course Hero uses AI to attempt to automatically extract content from documents to surface to you and others so you can study better, e.g., in search results, to enrich docs, and more. This preview shows page 1 - 2 out of 3 pages.

© Translational Cancer Research. All rights reserved.Transl Cancer Res2020;9(8):4473-4475 | The first clinical attempts to influence the detrimentalcourse of disease in glioblastoma (GBM) patients usingactive specific immunization strategies on the basis ofdendritic cell (DC) based vaccines date back to about20 years from here (1). A substantial number of small-scaleclinical trials using rather heterogeneous, non-standardizedDC-based vaccine products provided consistent data onoverall safety (2) and, at its best, indirect indications ofclinical effectiveness (3). Recently, Wenet al.(4) publishedtheir report on the results of a multi-center, randomizeddouble-blind, placebo-controlled phase IIb trial (RCT)of a DC vaccine, called ICT-107, in patients with newlydiagnosed GBM. As the authors rightfully state this isthe first, well-controlled, moderate-sized RCT in thispopulation showing a possible clinical benefit for a DCvaccine to date.ICT-107 contains autologous, monocyte-derived DCpulsed with a mixture of 6 well-known GBM-associatedtumor antigens, more specifically, synthetic 9–10 amino-acidpeptides to be presented in either an HLA-A1 ( MAGE-1and AIM-2) or an HLA-A2 (HER-2, TRP-2, gp100 andIL-13Ra2) context. For the maturation of the DC,interferon-gamma (IFN-γ) and lipopolysaccharide (LPS)where chosen in order to maximally shift the DC into aT-helper-type 1 (Th1) polarization. The choice for thisproduct specification suggests an “intermediate strategy”,holding the middle between “mono-peptide”-pulsedDC (with an inherently high chance to induce antigen-loss variants of the tumor and as such immune escape)and “whole-tumor-cell”-pulsed DC (with the notoriousdifficulty to adequately perform a specific immunemonitoring in the patients). Considering the fact that todate, there is no consensus on the optimal DC product,every choice inherently restricts the conclusions that can bedrawn from the trial results to the product itself. ICT-107is conceived only for GBM patients with an HLA-A1and/or HLA-A2 haplotype, accounting for roughly twothirds of the (Caucasian) population. Generalization andextrapolation to other DC vaccine products is to be avoided,although it would be very informative to be able to comparethe results of ICT-107 to these of the DCvax trial (5), ofwhich unfortunately only general survival data have beenreleased without any comparison of the different arms inthat randomized trial.The trial design consisted of a 2:1 randomization ofICT-107 versus control, the latter comprising theintradermal injections of autologous, mature, unpulsedDC at the same time-points as in the experimental arm.About two thirds of the postoperatively screened adultGBM patients in whom either a gross-total resection or alarge, subtotal resection (with a residual contrast-enhancingremnant of less than 1 cc) had been performed, seemedEditorial CommentaryVaccines against glioblastoma: reflections on the ICT-107 phaseIIb trialSteven De Vleeschouwer1,2,31Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium;2Laboratory of Experimental Neurosurgery and Neuroanatomy,Department of Neurosciences, KU Leuven, Leuven, Belgium;3Leuven Brain Institute (LBI), Leuven, BelgiumCorrespondence to:Steven De Vleeschouwer, MD, PhD. Department of Neurosurgery, UZ Leuven, Herestraat 49, B-3000 Leuven, Belgium. Email:

Upload your study docs or become a

Course Hero member to access this document

Upload your study docs or become a

Course Hero member to access this document

End of preview. Want to read all 3 pages?

Upload your study docs or become a

Course Hero member to access this document

Term
Winter
Professor
Tanmoy
Tags
Clinical trial

Newly uploaded documents

Show More

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture