https://scholars.lib.ntu.edu.tw/handle/123456789/376820
標題: | A DNA vaccine against cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) prevents tumor growth | 作者: | KENG-HSUEH LAN | 關鍵字: | Antigen-presenting cells (APC); Cytotoxic T-lymphocyte associated-antigen-4 (CTLA-4); Liposome; Vaccine | 公開日期: | 2013 | 卷: | 440 | 期: | 2 | 起(迄)頁: | 222-228 | 來源出版物: | Biochemical and Biophysical Research Communications | 摘要: | Co-stimulatory signaling pathway triggered by the binding of B7.1/B7.2 (CD80/86) of antigen-presenting cells (APCs) to CD28 of T cells is required for optimal T-cell activation. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding with a greater affinity. Ipilimumab, a monoclonal antibody against CTLA-4, has shown positive efficacy in a pivotal clinical trial for the treatment of metastatic melanoma and was approved by FDA. However, the cost of monoclonal antibody-based therapeutics might limit the number of patients treated. To develop a novel therapeutics specifically targeting CTLA-4, we constructed a DNA vaccine by cloning the sequence of CTLA-4 fused with a transmembrane domain sequence of placental alkaline phosphatase (PLAP) into a mammalian expression plasmid, pVAC-1. Immunization with the resulting construct, pVAC-1-hCTLA-4, elicited antibody specific to human CTLA-4 with cross reactivity to murine CTLA-4, which was sufficient for inhibiting B16F10 tumor growth in c57BL/6 mice in the absence of measurable toxicity. Coupling liposome with pVAC-1-mCTLA-4 could break tolerance to self-antigen in BALB/c mice and induce potent immunity against murine CTLA-4, and suppress growth of subcutaneous renal cell carcinoma (Renca). ? 2013 Elsevier Inc. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84885843997&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/376820 |
DOI: | 10.1016/j.bbrc.2013.09.031 | SDG/關鍵字: | alkaline phosphatase placenta isoenzyme; cytotoxic T lymphocyte antigen 4; DNA vaccine; liposome; animal cell; animal experiment; article; cancer cell culture; cancer immunotherapy; cross reaction; cytotoxicity; humoral immunity; immunization; immunogenicity; mouse; nonhuman; priority journal; tumor growth; Antigen-presenting cells (APC); Cytotoxic T-lymphocyte associated-antigen-4 (CTLA-4); Liposome; Vaccine; Animals; Antibodies, Monoclonal; Antigen-Presenting Cells; Carcinoma, Renal Cell; Cell Line, Tumor; CTLA-4 Antigen; Humans; Lymphocyte Activation; Melanoma; Mice; T-Lymphocytes, Cytotoxic; Vaccines, DNA; Mammalia; Murinae; Mus |
顯示於: | 腫瘤醫學研究所 |
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