The enhancing effect of DNA tetrahedron-based lactoferrin as an assembled adjuvant in immunotherapy

Abstract

Cancer immunotherapy faces significant challenges in enhancing immune responses, necessitating the development of innovative adjuvants. This study investigates the immune-stimulatory properties of Lactoferrin (LF) when assembled into a DNA tetrahedron structure (TAL) with stable spatial structure as an engineered adjuvant. This approach effectively addressed the limited immunostimulatory ability of lactoferrin in its free state, demonstrating the crucial role of DNA tetrahedron-based assembly of lactoferrin in enhancing adjuvant stimulation of antigen-presenting cells (APCs). TAL promoted antigen presentation, leading to a heightened inflammatory response in macrophage activation through the activation of the RIG-I-like receptor signaling pathway. In vivo studies further demonstrated that the assembled TAL enhanced immune response and exhibited substantial efficacy in enhancing synergy with Doxorubicin (DOX) in the context of cancer immunotherapy for breast cancer models. This synergy facilitated the differentiation of cytotoxic T lymphocytes and significantly amplified the therapeutic effect of DOX, allowing for a reduction in the required DOX dosage. Our findings suggest that TAL holds promise as a novel immune adjuvant in cancer immunotherapy, offering valuable insights for the development of neoadjuvants derived from biological nanomaterials. This study underscores the potential of strategically engineering weak immunostimulatory agents into stable structures to develop effective adjuvants, paving the way for innovative therapeutic strategies of adjuvant in clinical oncology.