Gas­filled ultrasound microbubbles enhance the immunoactivity of the HSP70­MAGEA1 fusion protein against MAGEA1­expressing tumours.

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 melanoma­associated antigen A1 (MAGEA1). Based on previous studies, gas­filled ultrasound microbubbles (MBs) were engineered to carry an HSP70­MAGEA1 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 HSP70­MAGEA1 fusion alone. Additionally, HSP70­MAGEA1 delivered via microbubbles clearly inhibited and delayed the growth of MAGEA1­expressing 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.