Nanoparticle delivery of recombinant IL-2 (BALLkine-2) achieves durable tumor control with less systemic adverse effects in cancer immunotherapy.

Recent strategies in cancer immunotherapy based on interleukin-2 (IL-2) are generally focused on reducing regulatory T cell (Treg) development by modifying IL-2 receptor alpha (IL-2Rα) domain. However, the clinical utility of high-dose IL-2 treatment is mainly limited by severe systemic toxicity. We find that peritumorally injectable 'BALLkine-2', recombinant human IL-2 (rIL-2) loaded porous nanoparticle, dramatically reduces systemic side effects of rIL-2 by minimizing systemic IL-2 exposure. Notably, in cynomolgus monkeys, subcutaneous (SC)-injection of BALLkine-2 not only dramatically reduces systemic circulation of rIL-2 in the blood, but also increases half-life of IL-2 compared to IV- or SC-injection of free rIL-2. Peritumorally-injected BALLkine-2 enhances intratumoral lymphocyte infiltration without inducing Treg development and more effectively synergizes with PD-1 blockade than high-dose rIL-2 administration in B16F10 melanoma model. BALLkine-2 could be a highly potent therapeutic option due to higher anti-tumor efficacy with lower and fewer doses and reduced systemic toxicity compared to systemic rIL-2.

A combination of Korean mistletoe extract and resistance exercise retarded the decline in muscle mass and strength in the elderly: A randomized controlled trial.

Given the increased concerns about the degenerative decline in the physical performance of the elderly, there is a need for developing effective strategies to suppress the age-related loss of skeletal muscle mass and functional capacity through a lifestyle intervention. This randomized controlled trial examined whether a combination of Korean mistletoe extract (KME) supplement and exercise affected muscle mass, muscle function, and targeted molecular expressions. Sixty-seven subjects aged 55-75years were assigned to placebo, low-dose (1g/d), or high-dose (2g/d) of KME for 12weeks. The body composition was significantly changed in the high-dose group during the intervention period as determined by skeletal muscle mass (P=0.040), fat free mass (P=0.042), soft lean mass (P=0.023), skeletal muscle index (P=0.041), fat-free mass index (P=0.030), percent body fat (P=0.044), and fat mass to lean mass ratio (P=0.030). Knee strength was measured by Cybex, demonstrating a significant effect in the KME groups compared to the placebo group (P=0.026 for peak torque and P=0.057 for set total work), which was more pronounced after adjusting for age, gender, protein, and energy intake (P=0.009 for peak torque and P=0.033 for set total work). The dynamic balance ability was remarkably improved in the high-dose group over a 12-week period as determined by Timed "Up and Go" (P=0.005 for fast walk test and P=0.024 for ordinary walk test). Consistent with these results, RT-PCR, multiplex analyses, and immunocytofluorescence staining revealed that a high-dose KME supplementation was effective for suppressing intracellular pathways related to muscle protein degradation, but stimulating those related to myogenesis. In particular, significant differences were found in atrogin-1 mRNA (P=0.002 at a single administration and P=0.001 at a 12-week administration), myogenin mRNA (P<0.0001 at a single administration and P=0.040 at a 12-week administration), and insulin growth factor 1 receptor phosphorylation (P=0.002 at a 12-week administration). These results suggest that KME supplementation together with resistance exercise may be useful in suppressing the age-related loss of muscle mass and strength in the elderly.