Department of Immunotherotherapeutics and Biotechnology, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX, 79601, United States.
Department of Immunotherotherapeutics and Biotechnology, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX, 79601, United States.
Pharmacol Res. 2021 Feb;164:105374. doi: 10.1016/j.phrs.2020.105374. Epub 2020 Dec 28.
Colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the United States despite an array of available treatment options. Current standard-of-care interventions for this malignancy include surgical resection, chemotherapy, and targeted therapies depending on the disease stage. Specifically, infusion of anti-vascular endothelial growth factor agents in combination with chemotherapy was an important development in improving the survival of patients with advanced colorectal cancer, while also helping give rise to other forms of anti-angiogenic therapies. Yet, one approach by which tumor angiogenesis may be further disrupted is through the administration of a dendritic cell (DC) vaccine targeting tumor-derived blood vessels, leading to cytotoxic immune responses that decrease tumor growth and synergize with other systemic therapies. Early generations of such vaccines exhibited protection against various forms of cancer in pre-clinical models, but clinical results have historically been disappointing. Sipuleucel-T (Provenge®) was the first, and to-date, only dendritic cell-based therapy to receive FDA approval after significantly increasing overall survival in prostate cancer patients. The unparalleled success of Sipuleucel-T has helped revitalize the clinical development of dendritic cell vaccines, which will be examined in this review. We also highlight the promise of these vaccines to instill anti-angiogenic immunity for individuals with advanced colorectal cancer.
尽管有多种治疗选择,但结直肠癌(CRC)在美国仍是导致癌症相关死亡的主要原因。目前,这种恶性肿瘤的标准治疗干预措施包括手术切除、化疗和靶向治疗,具体取决于疾病分期。具体而言,抗血管内皮生长因子药物与化疗联合使用是改善晚期结直肠癌患者生存的重要进展,同时也促使了其他形式的抗血管生成治疗的发展。然而,通过给予针对肿瘤源性血管的树突状细胞(DC)疫苗,可能进一步破坏肿瘤血管生成,从而引发细胞毒性免疫反应,减少肿瘤生长,并与其他全身治疗协同作用。此类疫苗的早期几代在临床前模型中显示出对各种癌症的保护作用,但历史上临床结果令人失望。Sipuleucel-T(Provenge®)是第一个也是迄今为止唯一一个获得 FDA 批准的基于树突状细胞的疗法,在前列腺癌患者中显著提高了总生存率。Sipuleucel-T 的空前成功帮助重振了树突状细胞疫苗的临床开发,本文将对此进行探讨。我们还强调了这些疫苗为晚期结直肠癌患者带来抗血管生成免疫的潜力。