Immunotherapies for cancer hold great promise for the future treatment of cancer. The successes
of these therapies, with some patients showing durable and complete remission, demonstrate the
power of harnessing the immune system to eradicate tumors. 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. In mammals, several forms of
cell death can occur, including apoptosis and ferroptosis. Since tumors often develop resistance to
apoptosis, triggering this process is not always the optimal strategy. That is why it is important to
find other ways to kill tumor cells by triggering cell death modalities separate from apoptosis. In our
preliminary data we have found that cancer cells undergoing ferroptotic cell death are nonimmunogenic,
thus limiting the induction of an efficient anti-tumor immune response. The major
goal of this proposal is to develop novel strategies to increase immunogenicity of ferroptotic cancer
cells, based on their encapsulation into microcapsules with intrinsic immunogenic properties. In
addition, we propose to co-encapsulate as a "bait" immune-stimulatory molecules (e.g. TLR
agonists) in nanocapsules to attract and activate dendritic cells. This 2-in-1 remedy should induce an
efficient anti-tumor immune response. This new approach could save lives.