2245P - Graphene oxide: A promising platform for delivery of cancer immunotherapy

Background

Nanomaterials have been proposed as antigen carriers in cancer immunotherapies, to increase target cell uptake and therapeutic efficacy, and reduce off-target toxicity. The 2-dimensional carbon nanomaterial graphene oxide (GO) possesses a large surface area and high peptide loading capacity, as well as being inexpensive and biodegradable. These properties promote the development of GO as a system for antigen loading and delivery in targeted cancer immunotherapy. We have investigated the potential of GO in enhancing immune cell activation and cytotoxicity, including its impact in combination therapy with checkpoint inhibitors.

Methods

GO was combined with ovalbumin (OVA) peptide (OVA_257-264) and the immununostimulant polyinosinic:polycytidylic acid (Poly (I:C)), a toll-like receptor 3 agonist. We assessed dendritic cell (DC) activation and OVA-specific T cell responses after subcutaneous injection of GO complexes into naïve mice with/without pre-transfer of OVA-specific OT-I CD8⁺ T cells. We also performed in vitro T cell activation assays by co-culturing DCs pre-stimulated with GO complexes with OT-I CD8⁺ T cells.

Results

GO without Poly (I:C) displayed minimal immunogenic potential. However, GO + Poly (I:C) significantly enhanced immune cell infiltration to the skin injection site by histology. We also found a significant increase in activation and migration of DCs to skin-draining lymph nodes in the mice receiving GO + Poly (I:C) 24 hours after injection. GO + Poly (I:C) also dramatically enhanced T cell expansion and cytotoxic responses in both spleen and draining lymph nodes 7 days after injection of mice that had previously received OT-I CD8⁺ T cells. Additionally, GO + Poly (I:C) significantly increased programmed death-1 (PD-1) expression on OT-I T cells in DC-OTI T cell co-cultures.

Conclusions

Our data have demonstrated the immunomodulatory potential of GO when complexed with Poly (I:C) by attracting immune cells including DCs to the injection site and boosting antigen-specific T cell cytotoxic responses in vivo and in vitro. DCs activated with GO complexed with Poly (I:C) increased PD-1 expression on T cells, which may suggest that graphene-based treatment could be beneficial in combination therapy with a checkpoint inhibitor such as anti-PD-1.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Engineering and Physical Sciences Research Council (EPSRC).

Disclosure

All authors have declared no conflicts of interest.