title: Anti-VEGFR2-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer.
abstract: Interferon-α (IFNα) has multiple antitumor effects including direct antitumor toxicity and the ability to potently stimulate both innate and adaptive immunity. However, its clinical applications in the treatment of malignancies have been limited because of short half-life and serious adverse reactions when attempting to deliver therapeutically effective doses. To address these issues, we fused IFNα2a to the anti-vascular endothelial growth factor and receptor 2 (VEGFR2) antibody JZA00 with the goal of targeting it to the tumor microenvironment where it can stimulate the antitumor immune response. The fusion protein, JZA01, is effective against colorectal cancer by inhibiting angiogenesis, exhibiting direct cytotoxicity, and activating the antitumor immune response. Although JZA01 exhibited reduced IFNα2 activityin vitrocompared with native IFNα2, VEGFR2 targeting permitted efficient antiproliferative, proapoptotic, antiangiogenesis, and immune-stimulating effects against the colorectal tumors HCT-116 and SW620. JZA01 showedin vivoefficacy in NOD-SCID mice-bearing established HCT-116 tumors. In conclusion, this study describes an antitumor immunotherapy that is highly promising for the treatment of colorectal cancer.
authors.affiliation: Antibody Engineering Laboratory, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing, China.
authors.forename: Zhaoting
authors.initials: Z
authors.lastname: Li
authors.affiliation: Antibody Engineering Laboratory, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing, China.
authors.forename: Yijia
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Antibody Engineering Laboratory, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles , Los Angeles, CA, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Trinh
authors.affiliation: Antibody Engineering Laboratory, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Ren
authors.affiliation: Antibody Engineering Laboratory, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing, China.
authors.forename: Fumou
authors.initials: F
authors.lastname: Sun
authors.affiliation: Antibody Engineering Laboratory, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing, China.
authors.forename: Youfu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Antibody Engineering Laboratory, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing, China.
authors.forename: Pengzhao
authors.initials: P
authors.lastname: Shang
authors.affiliation: Antibody Engineering Laboratory, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Antibody Engineering Laboratory, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles , Los Angeles, CA, USA.
authors.forename: Sherie L
authors.initials: SL
authors.lastname: Morrison
authors.affiliation: Antibody Engineering Laboratory, School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Nanjing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
keywords: CD8+ T cells; DCs; IFNα2; VEGFR2; colorectal cancer; tumor microenvironment