Aerosol delivery of interleukin-2 in combination with adoptive transfer of natural killer cells for the treatment of lung metastasis: Methodology and effect

Natural killer (NK) cells are a subtype of lymphocytes with a major role as a host defense mechanism against tumor cells. Allogeneic NK cell therapy is being used as an alternative promising therapy for many different cancers. Interleukin-2 (IL-2) is a critical cytokine for NK cell proliferation, survival, and effector functions. Cytokine support is essential to activate, expand, and increase the life span of NK cells. Aerosol delivery of IL-2 in combination with adoptive transfer of NK cells offers a reasonable approach for the treatment of lung metastases as it avoids the deleterious side effects of systemic IL-2. Using a human OS mouse model, we demonstrated the efficacy of this approach. Combination therapy of aerosol IL-2 with NK cells resulted in a better therapeutic effect against OS lung metastases as compared with each therapy alone. Aerosol IL-2 selectively increased infiltration, retention, and proliferation of infused NK cells in the lung, and there was no local inflammation or toxicity in the lungs or any other organ. Our results demonstrate that delivery of IL-2 via the aerosol route offers a feasible and innovative approach to enhance the immunotherapeutic effect of NK cells against pulmonary metastases. In the following chapter, we describe the methodology and effect of this innovative therapeutic approach.