Gas‑filled ultrasound microbubbles enhance the immunoactivity of the HSP70‑MAGEA1 fusion protein against MAGEA1‑expressing tumours

Gao,Xing; Nan,Yang; Yuan,Yuan; Gong,Xue; Sun,Yuanyuan; Zhou,Huihui; Zong,Yujin; Zhang,Lijun; Yu,Ming

doi:10.3892/mmr.2018.9003

Gas‑filled ultrasound microbubbles enhance the immunoactivity of the HSP70‑MAGEA1 fusion protein against MAGEA1‑expressing tumours

Authors:
- Xing Gao
- Yang Nan
- Yuan Yuan
- Xue Gong
- Yuanyuan Sun
- Huihui Zhou
- Yujin Zong
- Lijun Zhang
- Ming Yu
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Affiliations: State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Gynecology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China, Department of Ultrasound, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China, Department of Clinical Diagnosis, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
Published online on: May 9, 2018 https://doi.org/10.3892/mmr.2018.9003
Pages: 315-321
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Advanced malignant melanoma is characterized by rapid development, poor prognosis and insensitivity to chemoradiotherapy. Immunotherapy has become one of the primary clinical treatments for malignant melanomas. In recent decades, identifying specific tumour antigens and the enhanced immunoactivity of tumour vaccines has become critical for engineering successful tumour vaccines. As a widely used vaccine carrier, heat shock protein 70 (HSP70) clearly increases the immunogenicity of tumour antigens, such as melanoma‑associated antigen A1 (MAGEA1). Based on previous studies, gas‑filled ultrasound microbubbles (MBs) were engineered to carry an HSP70‑MAGEA1 fusion protein (FP). Following subcutaneous injection around the lymphatic nodes the FP was directly released into the lymph nodes under ultrasonic imaging. The results indicated that the microbubbles enhanced the immunoactivity of FPs more effectively than HSP70‑MAGEA1 fusion alone. Additionally, HSP70‑MAGEA1 delivered via microbubbles clearly inhibited and delayed the growth of MAGEA1‑expressing B16 melanomas in mice and improved the survival times of these animals compared with the fusion protein alone. The results of the present study demonstrated that controlled MBs enhance the immunoactivity of FPs and also highlights novel, potential vaccine carriers and a new strategy for engineering controllable tumour vaccine designs.

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