human anti-ccr4 minibody gene transfer for the treatment of cutaneous t-cell lymphoma人类anti-ccr4 minibody基因转移治疗皮肤t细胞淋巴瘤.pdfVIP

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human anti-ccr4 minibody gene transfer for the treatment of cutaneous t-cell lymphoma人类anti-ccr4 minibody基因转移治疗皮肤t细胞淋巴瘤.pdf

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human anti-ccr4 minibody gene transfer for the treatment of cutaneous t-cell lymphoma人类anti-ccr4 minibody基因转移治疗皮肤t细胞淋巴瘤

Human Anti-CCR4 Minibody Gene Transfer for the Treatment of Cutaneous T-Cell Lymphoma 1,2 1,2 1,2 1,2 1 Thomas Han , Ussama M. Abdel-Motal , De-Kuan Chang , Jianhua Sui , Asli Muvaffak , 3 1,2 3 1,2 James Campbell , Quan Zhu , Thomas S. Kupper *, Wayne A. Marasco * 1 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Department of Dermatology, Brigham and Women’s Hospital, Harvard Skin Disease Research Center, Harvard Medical School, Boston, Massachusetts, United States of America Abstract Background: Although several therapeutic options have become available for patients with Cutaneous T-cell Lymphoma (CTCL), no therapy has been curative. Recent studies have demonstrated that CTCL cells overexpress the CC chemokine receptor 4 (CCR4). Methodology/Principal Findings: In this study, a xenograft model of CTCL was established and a recombinant adeno- associated viral serotype 8 (AAV8) vector expressing a humanized single-chain variable fragment (scFv)-Fc fusion (scFvFc or ‘‘minibody’’) of anti-CCR4 monoclonal antibody (mAb) h1567 was evaluated for curative treatment. Human CCR4+ tumor- bearing mice treated once with intravenous infusion of AAV8 virions encoding the h1567 (AAV8-h1567) minibody showed anti-tumor activity in vivo and increased survival. The AAV8-h1567 minibody notably increased the number of tumor- infiltrating Ly-6G+ FccRII