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A Three-dimensional Thymic Culture System to Generate Murine Induced Pluripotent Stem Cell-derived Tumor Antigen-specific Thymic Emigrants
Published on: August 9, 2019
Antitumor and anti-angiogenesis immunity induced by CR-SEREX-identified Xenopus RHAMM
Han Shuo Yang1, Dong Mei Zhang, Hong Xin Deng
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. yhansh@scu.edu.cn
Immunization with xenogeneic antigens is an attractive approach to induce cross-reactive humoral and cellular immunity to inhibit tumor growth or angiogenesis. To identify novel xenogenic targets for immunotherapy, we have developed a modified serological expression cloning (SEREX) strategy, termed Cross-reactive SEREX (CR-SEREX). Among 78 positive clones identified by CR-SEREX, Xenopus receptor for hyaluronic-acid-mediated motility (xRHAMM) was most frequently identified (18 times), indicating the strongest immunogenic potential for xenogenic immunotherapy. A DNA vaccine based on xRHAMM effectively induced a protective antitumor immunity against local tumor and lung metastasis in B16 melanoma mouse models. Angiogenesis was inhibited and cell apoptosis was increased within tumors. Antitumor activity of xRHAMM worked through stimulation of an antigen-specific cellular response as well as through a specific humoral response against RHAMM, as confirmed by the depletion of immune cell subsets in vivo. Thus, a xenogenic vaccine based on xRHAMM induced an effective immunity against B16 melanoma cells and endothelial cells.
Immunization with xenogeneic antigens is an attractive approach to induce cross-reactive humoral and cellular immunity to inhibit tumor growth or angiogenesis. To identify novel xenogenic targets for immunotherapy, we have developed a modified serological expression cloning (SEREX) strategy, termed Cross-reactive SEREX (CR-SEREX). Among 78 positive clones identified by CR-SEREX, Xenopus receptor for hyaluronic-acid-mediated motility (xRHAMM) was most frequently identified (18 times), indicating the strongest immunogenic potential for xenogenic immunotherapy. A DNA vaccine based on xRHAMM effectively induced a protective antitumor immunity against local tumor and lung metastasis in B16 melanoma mouse models. Angiogenesis was inhibited and cell apoptosis was increased within tumors. Antitumor activity of xRHAMM worked through stimulation of an antigen-specific cellular response as well as through a specific humoral response against RHAMM, as confirmed by the depletion of immune cell subsets in vivo. Thus, a xenogenic vaccine based on xRHAMM induced an effective immunity against B16 melanoma cells and endothelial cells.

