screening of human tumor antigens for cd4+ t cell epitopes by combination of hla-transgenic mice, recombinant adenovirus and antigen peptide libraries人类肿瘤抗原的筛选cd4 + t细胞抗原表位的组合hla-transgenic老鼠,重组腺病毒和抗原肽库.pdfVIP

Screening of Human Tumor Antigens for CD4+ T Cell Epitopes by Combination of HLA-Transgenic Mice, Recombinant Adenovirus and Antigen Peptide Libraries 1 1. 3. 2 4 ¨ 5 Wolfram Osen , Sabine Soltek , Mingxia Song , Barbara Leuchs , Julia Steitz , Thomas Tuting , ¨ 1 6 3 3 Stefan B. Eichmuller , Xuan-Duc Nguyen , Dirk Schadendorf , Annette Paschen * 1 Clinical Cooperation for Unit Dermato-Oncology, German Cancer Research Center, Heidelberg, Germany, 2 Infection and Cancer Program, German Cancer Research Center, Heidelberg, Germany, 3 Department of Dermatology, University Hospital Essen, Essen, Germany, 4 Institute of Laboratory Animal Science and Experimental Surgery, RWTH-Aachen University, Aachen, Germany, 5 Department of Dermatology, University of Bonn, Bonn, Germany, 6 Institute for Immunology and Transfusion Medicine, Mannheim, Germany Abstract Background: As tumor antigen-specific CD4+ T cells can mediate strong therapeutic anti-tumor responses in melanoma patients we set out to establish a comprehensive screening strategy for the identification of tumor-specific CD4+ T cell epitopes suitable for detection, isolation and expansion of tumor-reactive T cells from patients. Methods and Findings: To scan the human melanoma differentiation antigens TRP-1 and TRP-2 for HLA-DRB1*0301-restricted CD4+ T cell epitopes we applied the following methodology: Splenocytes of HLA-DRB1*0301-transgenic mice immunized with recombinant adenovirus encoding TRP-1 (Ad5.TRP-1) or TRP-2 (Ad5.TRP-2) were tested for their T cell reactivity ag