Birrer Michael J, Fujiwara Keiichi, Oaknin Ana, Randall Leslie, Ojalvo Laureen S, Valencia Christian, Ray-Coquard Isabelle
Winthrop P. Rockefeller Cancer Institute, University of Arkansas Medical School, Little Rock, AR, United States.
Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
Front Oncol. 2022 Feb 23;12:814169. doi: 10.3389/fonc.2022.814169. eCollection 2022.
Cervical cancer is one of the most common and lethal cancers among women worldwide. Treatment options are limited in patients with persistent, recurrent, or metastatic cervical cancer, with <20% of women living >5 years. Persistent human papillomavirus (HPV) infection has been implicated in almost all cases of cervical cancer. HPV infection not only causes normal cervical cells to transform into cancer cells, but also creates an immunosuppressive environment for cancer cells to evade the immune system. Recent clinical trials of drugs targeting the PD-(L)1 pathway have demonstrated improvement in overall survival in patients with cervical cancer, but only 20% to 30% of patients show overall survival benefit beyond 2 years, and resistance to these treatments remains common. Therefore, novel treatment strategies targeting HPV infection-associated factors are currently being evaluated in clinical trials. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β "trap") fused to a human immunoglobulin G1 monoclonal antibody that blocks PD-L1. Early clinical trials of bintrafusp alfa have shown promising results in patients with advanced cervical cancer.
宫颈癌是全球女性中最常见且致命的癌症之一。对于持续性、复发性或转移性宫颈癌患者，治疗选择有限，只有不到20%的女性存活超过5年。几乎所有宫颈癌病例都与持续性人乳头瘤病毒（HPV）感染有关。HPV感染不仅会使正常宫颈细胞转变为癌细胞，还会为癌细胞创造一个免疫抑制环境以逃避免疫系统。近期针对PD-(L)1通路的药物临床试验表明，宫颈癌患者的总生存期有所改善，但只有20%至30%的患者在2年以上显示出总生存期获益，并且对这些治疗的耐药性仍然很常见。因此，目前正在临床试验中评估针对HPV感染相关因素的新型治疗策略。Bintrafusp alfa是一种一流的双功能融合蛋白，由TGF-βRII受体的细胞外结构域（一种TGF-β“陷阱”）与阻断PD-L1的人免疫球蛋白G1单克隆抗体融合而成。Bintrafusp alfa的早期临床试验在晚期宫颈癌患者中显示出了有前景的结果。
