Community Research and Development Information Service - CORDIS


GLYCOTREAT Report Summary

Project ID: 339977
Funded under: FP7-IDEAS-ERC
Country: Netherlands

Periodic Report Summary 2 - GLYCOTREAT (Novel vaccine generation for the treatment of cancer. A glyco-nanomedial approach instructing T cells)

The Glycotreat project aims to develop new glycan based nanomedicines to target to DC for the induction of powerful T-cell responses to treat cancer. In this project we focus on two types of cancer: one induced by viruses, and the other with a focus on self-antigen melanoma.
The project is divided into 3 work packages:
1. Glyco-chemical design and generation of nanomedicine.
2. The effective in situ activity of the vaccines in a human skin model.
3. The in-vivo activation of the nanomedicines to activate tumor specific CD4 and CD8 T-cell responses.

The task of the members of WP1 relates to the design of glycopeptides, multivalent glycopeptide networks and glycoliposomes. For this WP instrumentation is required; HPCL, peptide synthesizer, Dionex, which are all positioned at our department at VUmc. For WP2 the human in-vitro assays, flowcytometry, sorting, and imagestream analysis for routing of glycopeptides are studied within our equipment present in our flowcytometry unit. WP3 focusses on testing the glyco-tumor antigen formulations in mouse model systems. The mouse facility is hosting these activities, also tracking and microscopical analysis of the glyco antigens are performed. For these activities the microscopy unit has all microscope facilities operational for our research questions. All 3 WP’s made very good progress. In WP1 various glyco-nanomedicines were generated that vary in size and target potential for skin antigen presenting cells. This has allowed us to generate various glyco-nanomedicines that we can generate in large quantity to be tested in WP2 and WP3.

In WP2 the test of the various components in the human skin model was set out. As the glyco-nanomedicines have APC specific targeting potential, the human skin model can test the efficacy of these vaccines in more complex tissues. In vitro APC demonstrates targeting potential and increase of melanoma specific CD4 and CD8 T-cell responses. In situ skin experiments demonstrated the glycoliposomes to have anti-tumor activity. We elucidate whether antigen matrices (or branched MAPS) coupled with LeY can be bound and taken up via both DC-SIGN and Langerin on skin DC to induce anti-tumor T cell responses. We elucidate the (cross-)presenting route of (glyco)peptides in LC, where we already found routing to be initiated via early endosomes (Fehres et al 2015 CMI). Using high resolution imaging we aim to verify where (and when) the peptides are loaded on MHC I. In the coming time the human skin assay will be optimized to allow read-out of low antigen dose formulations of MAPS and determine the antigen presenting subset specificity for the MAPS and their potency to induce primary Mart-1 specific T cells. Moreover we are looking in detail to the intracellular routing of MAPS in DC and LC upon interacting DC-SIGN and Langerin respectively.

In WP3 we set out to test the glyco-nanomedicines for their in-vivo effectivity. We have demonstrated that increase in valence of glycans and tumor antigens increases the effectivity of tumor specific T-cells. In particular, we have focused on melanoma specific T-cells. We also investigated the influence of the tumor micro-environment on the potency to induce T-cell responses. We were very happy that the glyco-nanomedicines that we designed were very powerful. The in vivo responses are tested in a well-known melanoma model (B16). Moreover WP3 will focus on the analysis of duration and quality of the anti-tumor T-cell response induced, and will focus on revealing how these glyco-nanomedicines distribute in tissues in-vivo.

According to the Coordinator everything within the Glycotreat project goes smooth so far.

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