Authors: Yeon Jeong Yoo, Ryounho Eun, Hye Min Park, Suhyeon Kim, Sei Hyun Park, Janghun Heo, Yong Taik Lim
Published: 2023-11-15
Source: Full article
AbstractAlthough adoptive cell‐based therapy is illuminated as one of the promising approaches in cancer immunotherapy, it shows low antitumor efficacy because transferred cells adapt and alter toward a pro‐tumoral phenotype in response to the tumor's immunosuppressive milieu. Herein, nanoengineered macrophages anchored with functional liposome armed with cholesterol‐conjugated Toll‐like receptor 7/8 agonist (masked TLR7/8a, m7/8a) are generated to overcome the shortcomings of current macrophage‐based therapies and enhance the remodeling of the immunosuppressive tumor microenvironment (TME). The liposome‐anchored macrophages (LAMΦ‐m7/8a), are fabricated by anchoring dibenzocyclooctyne‐modified liposome(m7/8a) onto azido‐expressing macrophages via a bio‐orthogonal click reaction, are continuously invigorated due to the slow internalization of liposome(m7/8a) and sustained activation. LAMΦ‐m7/8a secreted ≈3 and 33‐fold more IL‐6 and TNF‐α than conventional M1–MΦ, maintained the M1 phenotype, and phagocytosed tumor cells for up to 48 h in vitro. Both intratumoral and intravenous injections of LAMΦ‐m7/8a induced effective antitumor efficacy when treated in combination with doxorubicin‐loaded liposomes in 4T1‐tumor bearing mice. It not only increases the infiltration of antigen‐specific CD8+ T cells secreting granzyme B, IFN‐γ, and TNF‐α within the TME, but also reduces myeloid‐derived suppressor cells. These results suggest that LAMΦ‐m7/8a may provide a suitable alternative to next‐generation cell‐based therapy platform.