Chimeric antigen receptor T (CAR T) cell therapy has achieved remarkable results treating patients with he-matological malignancies in clinical studies. Although promising, extensive research has also revealed that CAR T therapy is unsatisfactory for the treatment of solid tumors. In addition, the production of CAR T cells is time-consuming and it's hard for storage and transportation. In this work, inspired by the construction of CAR T cell, we developed an antibody-engineered exosomes from antigen-feeding dendritic cells for beyond CAR T therapy of solid tumor by in situ T cells activation and cancer cell targeting. We have confirmed that tumor antigen-stimulated dendritic cell-derived exosomes (tDC-Exo) provided major histocompatibility (MHC)-antigen com-plexes and CD86 co-stimulating molecules, which were the same as CAR of CAR T cell acting as the necessary signals for T cell activation. Furthermore, anti-CD3 and anti-EGFR were then engineered on tDC-Exo to promote the binding of T cell to cancer cells for precise therapy. Our CAR T cell therapy-mimicking system have shown an efficient endogenous T cells activation and their crosslinking with cancer cells for enhanced solid tumor therapy. More interestingly, we found that immune activation significantly up-regulated PD-L1 expression, and thus we confirmed the combination with anti-PD-L1 antibodies further enhanced the efficacy of our CAR T cell therapy-mimicking platform.
基金:
National Natural Science Foundation of China [21977024, 21601046, 31971304]; Beijing-Tianjin-Hebei Basic Research Cooperation Project [19JCZDJC64100]; Cross-Disciplinary Project of Hebei University [DXK201916]; One Hundred Talent Project of Hebei Province [E2018100002]; Medical Comprehensive Experimental Center of Hebei University
第一作者机构:[1]Hebei Univ, Coll Chem & Environm Sci, Chem Biol Key Lab Hebei Prov, Key Lab Med Chem & Mol Diag,Minist Educ, Baoding 071002, Peoples R China
通讯作者:
通讯机构:[2]Southern Med Univ, Affiliated Dongguan Hosp, Dongguan 523059, Peoples R China[3]Guangdong Prov Key Lab Shock & Microcirculat, Guangzhou 510515, Guangdong, Peoples R China[*1]College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of MedicinalChemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding, 071002, China
推荐引用方式(GB/T 7714):
Fan Miao,Liu Huifang,Yan Hongyu,et al.A CAR T-inspiring platform based on antibody-engineered exosomes from antigen-feeding dendritic cells for precise solid tumor therapy[J].BIOMATERIALS.2022,282:doi:10.1016/j.biomaterials.2022.121424.
APA:
Fan, Miao,Liu, Huifang,Yan, Hongyu,Che, Ruijun,Jin, Yi...&Li, Zhenhua.(2022).A CAR T-inspiring platform based on antibody-engineered exosomes from antigen-feeding dendritic cells for precise solid tumor therapy.BIOMATERIALS,282,
MLA:
Fan, Miao,et al."A CAR T-inspiring platform based on antibody-engineered exosomes from antigen-feeding dendritic cells for precise solid tumor therapy".BIOMATERIALS 282.(2022)