title: Therapeutic efficacy of an anti-PD-L1 antibody based immunocytokine in a metastatic mouse model of colorectal cancer.
abstract: Immunocytokines (antibody-cytokine fusions) have been proved to be a promising class of therapeutic agents for tumors. Anti-PD-L1 antibodies or IL-2 have been used to treat a variety of cancers. Here, in order to remove T cell inhibition and increasing the IL-2 concentration in the tumor microenvironment, we engineered a novel anti-PD-L1 antibody based immunocytokine by fusing hIL-2 to the C-Term of atezolizumab, denoted as BIPI. Our results revealed that BIPI was effective in stimulating T cell activation in vitro and could selectively localize to the tumor. Furthermore, tumor regression and prolonged survival were also observed in the metastatic colorectal cancer mouse model. The obviously longer survival mice in BIPI treatment group turned out depending on the function of CD8+T cells. The IFN- secreted from CD8+T cells in the spleen also contributed to the better tumor inhibition profile in BIPI treatment group than in anti-PD-L1 or IL-2 treatment alone. Taken together, our data evidenced the enhanced antitumor potency of BIPI, suggesting its potential use for cancers with a low response to the anti-PD-L1 or IL-2 treatment.
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, Shanghai, China; State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China; Shanghai Zhangjiang Biotechnology Co. Ltd, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, Shanghai, China; State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China.
authors.forename: Qingcheng
authors.initials: Q
authors.lastname: Guo
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, Shanghai, China; State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China; School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China; Shanghai Zhangjiang Biotechnology Co. Ltd, Shanghai, China.
authors.forename: Huaizu
authors.initials: H
authors.lastname: Guo
authors.affiliation: Shanghai Zhangjiang Biotechnology Co. Ltd, Shanghai, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China; Shanghai Zhangjiang Biotechnology Co. Ltd, Shanghai, China; School of Pharmacy, Liaocheng University, Liaocheng, China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China; Shanghai Zhangjiang Biotechnology Co. Ltd, Shanghai, China; Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos 138673, Singapore.
authors.forename: Weizhu
authors.initials: W
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China; Shanghai Zhangjiang Biotechnology Co. Ltd, Shanghai, China; School of Pharmacy, Liaocheng University, Liaocheng, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China; Shanghai Zhangjiang Biotechnology Co. Ltd, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China; Shanghai Zhangjiang Biotechnology Co. Ltd, Shanghai, China; School of Pharmacy, Liaocheng University, Liaocheng, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China; School of Pharmacy, Liaocheng University, Liaocheng, China; School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China; Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos 138673, Singapore. Electronic address: yguo_smmu@163.com.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Guo
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, Shanghai, China; State Key Laboratory of Antibody Medicine and Targeted Therapy, Shanghai, China; School of Pharmacy, Liaocheng University, Liaocheng, China. Electronic address: hwang_smmu@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D060890:B7-H1 Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016466:CHO Cells; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003412:Cricetulus; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D007376:Interleukin-2; D011994:Recombinant Proteins; C000594389:atezolizumab; D007371:Interferon-gamma
keywords: Anti-PD-L1; IL-2; Immunocytokine; Metastatic colorectal cancer; T cell activation; Tumor inhibition