Targeting phosphatidylserine to enhance immunogenicity of regulated necrotic cancer cells by microcapsules.

Cell-based immunotherapies hold great promise for the future treatment of cancer. The success of these therapies, with some patients showing durable and complete remission, demonstrate the power of harnessing the immune system to eradicate tumours. It is also becoming clear that the type of cancer cell death determines the antitumor immune response and, therefore, contributes to the efficiency of anti-cancer therapy and long-term survival of patients. Since tumors often develop resistance to apoptosis and necroptosis, triggering these processes is not always the optimal strategy. That is why it is crucial to select the proper cell death type that is able to induce potent and strong anti-cancer immune responses, potentially leading to tumour eradication. My preliminary data indicate that initially non-immunogenic ferroptotic cancer cells can be converted to immunogenic cell death by targeting phosphatidylserine with anneixn-V on ferroptotic cells. Thus, the major goal of this proposal is to develop novel strategies to increase immunogenicity of ferroptotic cancer cells, based on recombinant annexin-V encapsulation into microcapsules, and validate this approach in in situ therapeutic vaccination. This new approach could save lives.