Synergic Chemoimmunotherapy of Cervical Cancer by Combining Cisplatin with Thermosensitive Polypeptide Fused Interferon Alpha

Abstract

AbstractCervical cancer is the fourth most common female malignancy. Surgery and concurrent chemoradiotherapy are the main treatment methods. Although immunotherapy and targeted therapy have made tremendous progress in cancer therapy, they show limited therapeutic effects in treating advanced or recurrent cervical cancer. In this study, a first‐line drug for cervical cancer chemotherapy, cisplatin, is combined with a modified immunomodulatory agent, interferon‐alpha genetically fused to a thermosensitive polypeptide, for synergistic immunochemotherapy of cervical cancer. The unique thermosensitivity of the fusion protein makes it possible to greatly improve the pharmacokinetics of interferon‐alpha, leading to increased tumor accumulation and thus enhanced antitumor efficiency in mice bearing cervical cancers. Moreover, the combination of the fusion protein and cisplatin can inhibit the development of cervical cancer much more effectively than the fusion protein alone, cisplatin alone, or interferon‐alpha plus cisplatin, demonstrating the enhanced synergistic effect of the fusion protein plus cisplatin in cervical cancer immunochemotherapy over interferon‐alpha plus cisplatin. These results show that the synergistic combination of thermosensitive polypeptide fused interferon‐alpha and cisplatin can provide an effective and promising strategy for cervical cancer.