Multifunctional Enzyme Nanocapsules Boost T Cell Immunity and Multifunctional Enzyme Nanocapsules Boost T Cell Immunity and Efficacy of Cancer Immunotherapy

Cancer immunotherapy has reshaped the landscape of cancer treatment, but its effectiveness is limited by tumor immunosuppression caused by excessive lactate production by cancer cells. While efforts to reduce lactate levels through lactate dehydrogenase inhibition have been made, such inhibitors can disrupt the metabolism of healthy cells and cause severe non-specific toxicity. Based on lactate oxidase, we report herein an enzyme therapeutic, which reduces lactate levels, releases an immunostimulatory molecule-hydrogen peroxide, averts tumor immunosuppression, and synergistically improves the efficacy of immune checkpoint blockades, as demonstrated in a murine melanoma model and a humanized mouse model of triple-negative breast cancer. Overall design: Single-cell RNA seq of tumor cells treated with and without nanoparticles