Multivalent Carbohydrate Nanocomposites for Tumor Microenvironment Remodeling to Enhance Antitumor Immunity

Gyu Hwan Hyun, Da-Hye Jeong, Yoon Young Yang, In Ho Cho, Yu-Jin Ha, Xiaohui Xing, D Wade Abbott, Yves S Y Hsieh, Yun Pyo Kang, Jong-Ho Cha, Soon-Sun Hong, Seul Ji Lee, You-Sun Kim, Sung Won Kwon

研究成果: 雜誌貢獻文章同行評審


Current cancer immunotherapeutic strategies mainly focus on remodeling the tumor microenvironment (TME) to make it favorable for antitumor immunity. Increasing attention has been paid to developing innovative immunomodulatory adjuvants that can restore weakened antitumor immunity by conferring immunogenicity to inflamed tumor tissues. Here, a galactan-enriched nanocomposite (Gal-NC) is developed from native carbohydrate structures through an optimized enzymatic transformation for effective, stable, and biosafe innate immunomodulation. Gal-NC is characterized as a carbohydrate nanoadjuvant with a macrophage-targeting feature. It is composed of repeating galactan glycopatterns derived from heteropolysaccharide structures of plant origin. The galactan repeats of Gal-NC function as multivalent pattern-recognition sites for Toll-like receptor 4 (TLR4). Functionally, Gal-NC-mediated TLR activation induces the repolarization of tumor-associated macrophages (TAMs) toward immunostimulatory/tumoricidal M1-like phenotypes. Gal-NC increases the intratumoral population of cytotoxic T cells, the main effector cells of antitumor immunity, via re-educated TAMs. These TME alterations synergistically enhance the T-cell-mediated antitumor response induced by αPD-1 administration, suggesting that Gal-NC has potential value as an adjuvant for immune checkpoint blockade combination therapies. Thus, the Gal-NC model established herein suggests a glycoengineering strategy to design a carbohydrate-based nanocomposite for advanced cancer immunotherapies.
頁(從 - 到)11567–11582
期刊ACS Nano
出版狀態已發佈 - 6月 27 2023


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