title: Retargeted human avidin-CAR T cells for adoptive immunotherapy of EGFRvIII expressing gliomas and their evaluation via optical imaging.
abstract: There has been significant progress in the design of chimeric antigen receptors (CAR) for adoptive immunotherapy targeting tumor-associated antigens. However, the challenge of monitoring the therapy in real time has been continually ignored. To address this issue, we developed optical molecular imaging approaches to evaluate a recently reported novel CAR strategy for adoptive immunotherapy against glioma xenografts expressing EGFRvIII. We initially biotinylated a novel anti-EGFRvIII monoclonal antibody (biotin-4G1) to pre-target EGFRvIII+ gliomas and then redirect activated avidin-CAR expressing T cells against the pre-targeted biotin-4G1. By optical imaging study and bio-distribution analysis, we confirmed the specificity of pre-target and target and determined the optimal time for T cells adoptive transfer in vivo. The results showed this therapeutic strategy offered efficient therapy effect to EGFRvIII+ glioma-bearing mice and implied that optical imaging is a highly useful tool in aiding in the instruction of clinical CAR-T cells adoptive transfer in future.
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Radiological Medicine, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Xujie
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Radiological Medicine, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Cell Biology, Peking University Health Science Center, Beijing, People's Republic of China.|Peking University Stem Cell Research Center, Beijing, People's Republic of China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Cell Biology, Peking University Health Science Center, Beijing, People's Republic of China.|Peking University Stem Cell Research Center, Beijing, People's Republic of China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Chinese PLA Navy General Hospital, Beijing, People's Republic of China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Chinese PLA Navy General Hospital, Beijing, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Beijing Cellonis Biotechnologies Co., Ltd, Zhongguancun Bio-Medicine Park, Beijing, People's Republic of China.
authors.forename: Limin
authors.initials: L
authors.lastname: Hao
authors.affiliation: Beijing Cellonis Biotechnologies Co., Ltd, Zhongguancun Bio-Medicine Park, Beijing, People's Republic of China.
authors.forename: Guoqiu
authors.initials: G
authors.lastname: Lu
authors.affiliation: Beijing Cellonis Biotechnologies Co., Ltd, Zhongguancun Bio-Medicine Park, Beijing, People's Republic of China.
authors.forename: Kangcheng
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Beijing Cellonis Biotechnologies Co., Ltd, Zhongguancun Bio-Medicine Park, Beijing, People's Republic of China.
authors.forename: Xikui
authors.initials: X
authors.lastname: Gong
authors.affiliation: Beijing Cellonis Biotechnologies Co., Ltd, Zhongguancun Bio-Medicine Park, Beijing, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Medical Isotopes Research Center, Peking University, Beijing, People's Republic of China.|Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Peking University Health Science Center, Beijing, People's Republic of China.|Peking University Stem Cell Research Center, Beijing, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology; D001360:Avidin / Q000235:genetics / Q000276:immunology; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D005260:Female; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D011946:Receptors, Antigen / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D016207:Cytokines; D011946:Receptors, Antigen; D011993:Recombinant Fusion Proteins; C410723:epidermal growth factor receptor VIII; D001360:Avidin; D066246:ErbB Receptors
keywords: EGFRvIII; adoptive immunotherapy; avidin-CAR; biotinylated; optical imaging