Approaching antigen-presenting cell immunotherapy for cervical cancers using single-cell transcriptomics (2017-2019)

Cancers induce immunosuppressive mechanisms, and immunotherapy can either alleviate immunosuppression or activate tumor antigen-specific immunity. Infection with `high-risk¿ Human papillomaviruses (HPVs) is also associated induction of local immunosuppression and development of cancers. However, current HPV prophylactic vaccines are ineffective in patients with pre-existing infections. Immunotherapy for persisting HPV infection will be of considerable clinical value, and will become feasible if the underlying immunological dynamics are better understood. Most immunotherapies rely on functional professional antigen-presenting cells (APCs) to trigger anti-tumor effects. Thus, APCs control the immunological program that will determine the success or failure of immunotherapy. Queensland-based Admedus Immunotherapies and Professor Ian Frazer has identified that revitalizing APCs to induce cell-mediated immunity against HPV infection may be of significant therapeutic potential. We will adopt cutting-edge single-cell RNA-sequencing technology to assess APC biology in an HPV-associated immunosuppressive pre-cancer mouse model and test APC-based immunotherapy strategies in extensive and close collaboration with Admedus Immunotherapies based on the findings. This project will bridge a critical unmet medical need in treating afflicted patients in Queensland and will have long term benefits in improving the overall health of Queenslanders. Successful completion will reinforce Queensland¿s position as a world-class hub for translational biomedical research and innovation