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Devising a glycoantigen specific DC immunotherapy to develop an efficient anti-tumor response within the hypoxic environment of glioblastoma (TUM2P.1026)
Journal article   Open access   Peer reviewed

Devising a glycoantigen specific DC immunotherapy to develop an efficient anti-tumor response within the hypoxic environment of glioblastoma (TUM2P.1026)

Rashida Ginwala, Divya Sagar, Xiaofang Huang, Catherine Foss, Sergey Karakashev, Zafar Khan, Ramila Philip, Martin Pomper, Mauricio Reginato and Pooja Jain
The Journal of immunology (1950), v 194(1_Supplement), 69.23
01 May 2015
DOI: https://doi.org/10.4049/jimmunol.194.Supp.69.23
url
https://doi.org/10.4049/jimmunol.194.Supp.69.23View
Published, Version of Record (VoR)CC BY-NC-ND V4.0,  Open

Abstract

Abstract Glioblastoma (GBM) is the most malignant type of brain tumor, its therapy hindered by the hypoxic microenvironment that promotes tumor resistance and inhibits immune cell function. We propose combining dendritic cell (DC) immunotherapy with hypoxia reversal to eradicate GBM. HIF-1α, a transcription factor that stimulates genes promoting angiogenesis and tumor growth, was expressed in both GBM cells and DCs under hypoxia. Hypoxia also downregulated expression of HLA-DR, CD86 and HLA-ABC on DCs affecting their antigen processing and presentation capability in addition to reducing the generation of pro-inflammatory cytokines such as TNF- α and IL-6. In vivo imaging revealed fluorescently labeled DCs migrating away from site of injection into spleen and mediastinal lymph nodes of mice with GBM indicating chemoattraction of DCs to areas of inflammation post hypoxia reversal using using antisense HIF-1α plasmid. In order to identify tumor antigens we used glycan analysis wherein GlcNAc was overexpressed in hypoxic GBM cells. We then enriched GlcNAc expressing glycoantigens and identified 46 glycopeptides derived from 33 glycoproteins. Amongst them Lamb1, SerpinH1, CD63 and others are associated with tumor survival, progression, invasion, immune evasion and therapy resistance. Lectins expressed on DCs complimentary to these glycans will be identified to devise a DC based vaccine, which in conjunction with hypoxia reversal will augment the efficacy of existing therapies against GBM.

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