Enhanced Proliferation and Activation of Natural Killer Cells by Deer Antler Velvet Extract, YC-1101, and Its Synergistic Antitumor Effects in CT26 Syngeneic Mouse Model

Deer antler velvet (<i>Cervus elaphus</i> L.) is a traditional material in oriental medicine, extensively utilized for its anti-aging, antioxidant, and immune-boosting properties. Our prior research revealed that enzyme-derived deer antler velvet extract (YC-1101) stimulated the immune system by activating macrophages and augmenting splenocyte proliferation. In this study, we investigated the effect of YC-1101 on the proliferation, activation, and cytotoxicity of natural killer (NK) cells, emphasizing activation-receptor upregulation, cytokine secretion, and antitumor efficacy. Our findings demonstrated that YC-1101 treatment markedly enhanced NK cell proliferation in a dose-dependent and time-dependent manner by preserving mitochondrial function. NK cells expanded through YC-1101 treatment exhibited a significant increase in surface expression of activating NK receptors, NKG2D, and NKp44. Additionally, levels of immune-related cytokines like tumor necrosis factor-alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor were substantially elevated in the YC-1101-treated group compared with control. Notably, NK cell activation induced by YC-1101 intensified cytotoxicity against various cancer cell lines, and combining YC-1101 with immune checkpoint inhibition synergistically enhanced antitumor activity. Collectively, our results indicate that integration of YC-1101 with expanded NK cells could be a promising approach to augment cancer treatment efficacy.