Precision glycocalyx editing as a strategy for cancer immunotherapy.
Han Xiao,Elliot C. Woods,Elliot C. Woods,Petar Vukojicic,Petar Vukojicic,Carolyn R. Bertozzi,Carolyn R. Bertozzi +6 more
TLDR
Development of antibody–sialidase conjugates that enhance tumor cell susceptibility to antibody-dependent cell-mediated cytotoxicity (ADCC) by selective desialylation of the tumor cell glycocalyx is reported.Abstract:
Cell surface sialosides constitute a central axis of immune modulation that is exploited by tumors to evade both innate and adaptive immune destruction. Therapeutic strategies that target tumor-associated sialosides may therefore potentiate antitumor immunity. Here, we report the development of antibody–sialidase conjugates that enhance tumor cell susceptibility to antibody-dependent cell-mediated cytotoxicity (ADCC) by selective desialylation of the tumor cell glycocalyx. We chemically fused a recombinant sialidase to the human epidermal growth factor receptor 2 (HER2)-specific antibody trastuzumab through a C-terminal aldehyde tag. The antibody–sialidase conjugate desialylated tumor cells in a HER2-dependent manner, reduced binding by natural killer (NK) cell inhibitory sialic acid-binding Ig-like lectin (Siglec) receptors, and enhanced binding to the NK-activating receptor natural killer group 2D (NKG2D). Sialidase conjugation to trastuzumab enhanced ADCC against tumor cells expressing moderate levels of HER2, suggesting a therapeutic strategy for cancer patients with lower HER2 levels or inherent trastuzumab resistance. Precision glycocalyx editing with antibody–enzyme conjugates is therefore a promising avenue for cancer immune therapy.read more
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Nanotechnology for Multimodal Synergistic Cancer Therapy
TL;DR: In this review, state-of-the-art studies concerning recent advances in nanotechnology-mediated multimodal synergistic therapy will be systematically discussed, with an emphasis on the construction of multifunctional nanomaterials for realizing bimodal and trimodal synergy therapy.
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Fenton-Reaction-Acceleratable Magnetic Nanoparticles for Ferroptosis Therapy of Orthotopic Brain Tumors.
Zheyu Shen,Zheyu Shen,Ting Liu,Yan Li,Joseph Lau,Zhen Yang,Wenpei Fan,Zijian Zhou,Changrong Shi,Chaomin Ke,Vladimir I. Bregadze,Swadhin K. Mandal,Yijing Liu,Zihou Li,Ting Xue,Guizhi Zhu,Guizhi Zhu,Jeeva Munasinghe,Gang Niu,Aiguo Wu,Xiaoyuan Chen +20 more
TL;DR: Fenton-reaction-acceleratable magnetic nanoparticles, i.e., cisplatin (CDDP)-loaded Fe3O4/Gd2O3 hybrid nanoparticles with conjugation of lactoferrin (LF) and RGD dimer (RGD2), were exploited in this study for FT of orthotopic brain tumors and led to significant inhibition of tumor growth.
Journal ArticleDOI
Eradication of Triple-Negative Breast Cancer Cells by Targeting Glycosylated PD-L1.
Chia Wei Li,Seung Oe Lim,Ezra M. Chung,Kim Yong Soo,Andrew H. Park,Jun Yao,Jong Ho Cha,Weiya Xia,Li Chuan Chan,Taewan Kim,Shih Shin Chang,Heng Huan Lee,Chao Kai Chou,Yen-Liang Liu,Hsin-Chih Yeh,Evan P. Perillo,Andrew K. Dunn,Chu Wei Kuo,Kay-Hooi Khoo,Jennifer L. Hsu,Yun Wu,Jung Mao Hsu,Hirohito Yamaguchi,Tzu Hsuan Huang,Aysegul A. Sahin,Gabriel N. Hortobagyi,Stephen S. Yoo,Mien Chie Hung +27 more
TL;DR: Targeting protein glycosylation as a potential strategy to enhance immune checkpoint therapy is suggested, as it remains largely unknown whether the sugar moiety contributes to immunosuppression.
Journal ArticleDOI
Glycosylation in the Era of Cancer-Targeted Therapy: Where Are We Heading?
TL;DR: This review provides insights on the impact of glycosylation in cancer biology and its influence in the current approaches of targeted cancer therapies in the clinical setting, outlining potential applications of glycan-based biomarkers for patient stratification and strategies for improving personalized cancer treatment.
Journal ArticleDOI
The tumour glyco-code as a novel immune checkpoint for immunotherapy.
TL;DR: How the tumour 'glyco-code' modifies immunity and suggest that targeting glycans could offer new therapeutic opportunities is highlighted.
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