Cancer Vaccines
Personalized neoantigen vaccines are emerging as a class of highly promising immunotherapy. Although vaccination against infection-associated tumours for cancer prevention has been successful, progress for vaccination against non-infectious tumours, which make up the majority of the cancers, is impeded by limited immunogenicity. By harnessing the power of new genomic technologies, scientists are now better equipped to re-interrogate the cancer neoantigen landscape, and in a patient-specific manner. Neoantigens are antigens that arise from mutations in cancer cells that are not present in normal cells. They thus represent excellent targets for immunotherapy due to their specific expression in tumour cells and potential lack of side effects. Indeed, recent clinical trials showed that neoantigen vaccines exhibit high clinical efficacy, and are lauded to be a game-changer for cancer treatment. Despite remarkable success in early clinical trials, there are challenges that will potentially impede clinical implementation of cancer vaccines. Thus, we seek to identify and address current gaps in cancer vaccine development. Leveraging on the ability of stem cells to generate multiple types, we will engineer and differentiate stem cells into cells capable of activating cytotoxic T-cells, the primary tumour-killing cells. Specifically, we aim to generate a highly versatile and scalable ‘off-the-shelf’ source of artificial antigen-presenting cells starting from genetically engineered induced pluripotent stem cells. This technology circumvents the problems associated with dendritic cell vaccine delivery and further provides a platform to rapidly screen and select immunogenic tumour-specific neoantigens for clinical applications. The overarching goal is to address critical steps in improving the efficacy of neoantigen vaccines, with the ultimate aim of translating the research findings into clinical practice and personalizing cancer treatment.