Potent antitumor efficacy of ex vivo expanded and cryopreserved human natural killer cells against orthotopic pancreatic cancer

Background & Aim Natural killer (NK) cells are specialized components of the innate immune system that contribute to the first line of defense against viral infections and cancer. Ex vivo expanded NK cells are a promising tool for the use in adoptive immunotherapy. Pancreatic cancer is one of the most aggressive tumor types and severely limits the therapeutic efficacy of both immunotherapeutics and conventional chemotherapeutics because ECM act as a major physical barrier against drug penetration. Methods, Results & Conclusion To address these challenges, we expanded and cryopreserved allogeneic NK cells. And cryopreserved NK cells were evaluated for their therapeutic efficacy against desmoplastic pancreatic tumors, ultimately aiming to develop easily accessible and mass-producible off-the-shelf cell-based immunotherapeutics. Ex vivoexpanded and cryopreserved cells retained highly pure and activated population of NK cells. In addition, ex vivo expanded and cryopreserved NK cells exhibited not only potent killing activity and cytokine production against various pancreatic cancer cell lines in vitro but also excellent tumor growth suppression in vivo orthotopic pancreatic cancer model. In conclusion, ex vivo expanded and cryopreserved NK cells are a strong candidate for future cell-mediated systemic immunotherapy against pancreatic cancer. Natural killer (NK) cells are specialized components of the innate immune system that contribute to the first line of defense against viral infections and cancer. Ex vivo expanded NK cells are a promising tool for the use in adoptive immunotherapy. Pancreatic cancer is one of the most aggressive tumor types and severely limits the therapeutic efficacy of both immunotherapeutics and conventional chemotherapeutics because ECM act as a major physical barrier against drug penetration. To address these challenges, we expanded and cryopreserved allogeneic NK cells. And cryopreserved NK cells were evaluated for their therapeutic efficacy against desmoplastic pancreatic tumors, ultimately aiming to develop easily accessible and mass-producible off-the-shelf cell-based immunotherapeutics. Ex vivoexpanded and cryopreserved cells retained highly pure and activated population of NK cells. In addition, ex vivo expanded and cryopreserved NK cells exhibited not only potent killing activity and cytokine production against various pancreatic cancer cell lines in vitro but also excellent tumor growth suppression in vivo orthotopic pancreatic cancer model. In conclusion, ex vivo expanded and cryopreserved NK cells are a strong candidate for future cell-mediated systemic immunotherapy against pancreatic cancer.