Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Apr 26:8:127.
doi: 10.3389/fonc.2018.00127. eCollection 2018.

Immune Response Generated With the Administration of Autologous Dendritic Cells Pulsed With an Allogenic Tumoral Cell-Lines Lysate in Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

Daniel Benitez-Ribas  1 , Raquel Cabezón  1 , Georgina Flórez-Grau  1 , Mari Carmen Molero  2 , Patricia Puerta  3 , Antonio Guillen  3 , Sonia Paco  4   5 , Angel M Carcaboso  4   5 , Vicente Santa-Maria Lopez  5   6 , Ofelia Cruz  5   6 , Carmen de Torres  4   5 , Noelia Salvador  4   5 , Manel Juan  1   7 , Jaume Mora  4   5 , Andres Morales La Madrid  4   5   6
Affiliations

Immune Response Generated With the Administration of Autologous Dendritic Cells Pulsed With an Allogenic Tumoral Cell-Lines Lysate in Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

Daniel Benitez-Ribas et al. Front Oncol. .

Erratum in

Abstract

Background and objective: Diffuse intrinsic pontine glioma (DIPG) is a lethal brainstem tumor in children. Dendritic cells (DCs) have T-cell stimulatory capacity and, therefore, potential antitumor activity for disease control. DCs vaccines have been shown to reactivate tumor-specific T cells in both clinical and preclinical settings. We designed a phase Ib immunotherapy (IT) clinical trial with the use of autologous dendritic cells (ADCs) pulsed with an allogeneic tumors cell-lines lysate in patients with newly diagnosed DIPG after irradiation (radiation therapy).

Methods: Nine patients with newly diagnosed DIPG met enrollment criteria. Autologous dendritic cell vaccines (ADCV) were prepared from monocytes obtained by leukapheresis. Five ADCV doses were administered intradermally during induction phase. In the absence of tumor progression, patients received three boosts of tumor lysate every 3 months during the maintenance phase.

Results: Vaccine fabrication was feasible in all patients included in the study. Non-specific KLH (9/9 patients) and specific (8/9 patients) antitumor response was identified by immunologic studies in peripheral blood mononuclear cells (PBMC). Immunological responses were also confirmed in the T lymphocytes isolated from the cerebrospinal fluid (CSF) of two patients. Vaccine administration resulted safe in all patients treated with this schema.

Conclusion: These preliminary results demonstrate that ADCV preparation is feasible, safe, and generate a DIPG-specific immune response detected in PBMC and CSF. This strategy shows a promising backbone for future schemas of combination IT.

Keywords: cell; dendritic; diffuse intrinsic pontine glioma; immunotherapy; vaccination.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Therapeutic schema.
Figure 2
Figure 2
Consort diagram.
Figure 3
Figure 3
Characterization of dendritic cells (DCs) vaccines. (A) Increased expression of CD80, CD83, MHC class II, and CCR7 molecules on DCs surface membrane of autologous dendritic cell (ADC) compared to immature DC used as negative control. (B) Increased intensity of molecules (MFI) of ADC after stimulation compared to immature DC used as negative control.
Figure 4
Figure 4
Isolated and expanded T-cell obtained from CFS. (A) Antigen specificity of T cell from CSF was evaluated by cell proliferation (cpm indicates thymidine incorporation; cpm = counts per million) in response to KLH or tumor cell lines lysate. (B) T cell activation was measured by cytokine production (IFN-γ) in response to KLH or tumor cell lines lysate compared to negative.
See this image and copyright information in PMC

References

    1. Robison NJ, Kieran MW. Diffuse intrinsic pontine glioma: a reassessment. J Neurooncol (2014) 119(1):7–15.10.1007/s11060-014-1448-8 - DOI - PubMed
    1. Khuong-Quang D-A, Buczkowicz P, Rakopoulos P, Liu X-Y, Fontebasso AM, Bouffet E, et al. K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol (2012) 124(3):439–47.10.1007/s00401-012-0998-0 - DOI - PMC - PubMed
    1. Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L, Dzamba M, et al. Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet (2014) 46(5):451–6.10.1038/ng.2936 - DOI - PMC - PubMed
    1. Taylor KR, Mackay A, Truffaux N, Butterfield YS, Morozova O, Philippe C, et al. Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat Genet (2014) 46(5):457–61.10.1038/ng.2925 - DOI - PMC - PubMed
    1. Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, et al. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet (2014) 46(5):444–50.10.1038/ng.2938 - DOI - PMC - PubMed