<p>Despite recent advancements in immunotherapy, most cancer patients still struggle to achieve sustained benefits, highlighting the need for new treatment strategies. In the past, lack of available models to assess immunotherapeutic combinations hampered development. In this new study, we utilized a novel all-autologous humanized melanoma mouse model to assess the efficacy of NT-I7 (human-reagent grade, efineptakin alfa), a long-acting human IL-7. Given that NT-I7 has been shown to enhance T cell proliferation and survival in both humans and mice, we hypothesized that NT-I7 would improve the engraftment of patient immune cells and the effectiveness of anti-PD-1 therapy in our humanized melanoma model, which was reported to accurately mimic actual clinical outcome, providing more precise assessment of clinical efficacy and relevance. Our findings indicate that NT-I7 significantly enhances T cell engraftment. We discovered a synergistic effect between NT-I7 and anti-PD-1 (Pembrolizumab) that notably augments immunotherapeutic efficacy through the expansion of T_CM cells and sustained cytotoxicity. In sum, our humanized model reveals that NT-I7 holds great promise as a next-generation therapy to enhance clinical responses and patient care.</p>